Automated immunoassay analyzer

ABSTRACT

An improved automated immunoassay analyzer including a high throughput automated immunoassay system which can perform high volume testing on a broad range of analytes while selecting from among a diverse set of immunoassays for any given sample. The immunoanalyzer has the capacity to perform a wide range of different types of immunoassays by facile storage and automated combination aboard the instrument among a wide variety of different types of reagents and heterogenous immunoassay beads stored on-board the instrument. The automated design allows reduced user interface (e.g., tests are performed automatically from computer input) including the ability to order, perform and reassay tests reflexively based on test results without operator intervention. Further, the inventive analyzer is not sample tube specific; that is, an instrument that can accept sample tube sizes within a broad size range. The inventive automated immunoassay analyzer also provides a re-useable sample dilution well, and a high speed bead washing station that eliminates the need for assay tubes having integral, waste fluid collection chambers.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation application of U.S. patentapplication Ser. No. 08/672,654 filed on Jun. 28, 1996, now U.S. Pat.No. 5,885,529 and the complete contents of that application is hereinincorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention is generally relates to an automated immunoassayanalyzer and, more particularly, to a high throughput automatedimmunoassay analyzer which permits high volume assay of a broad range ofanalytes in bodily fluids.

2. Description of the Prior Art

An immunoassay is a well known laboratory method used to determine theamount of an analyte in a sample such as plasma or urine. It is based onthe interaction of antibodies with antigens, and because of the degreeof selectivity for the analyte (either antigen or antibody), animmunoassay can be used to quantitatively determine very lowconcentrations of drugs, hormones, polypeptides, or other analytecompounds found in a test sample. For many years, immunoassays wereperformed by hand by trained laboratory technicians.

More recently, many companies have begun producing automated immunoassayanalyzers. Automating the immunoassay procedures can be onerous becauseof the large number of steps needed to be executed. For example, in aconventional scheme, a sample is mixed with a reagent and a solidsupport having a bound antigen or antibody, the sample is incubated suchthat the corresponding antigen or antibody in the sample and a labeledantigen or antibody provided in the reagent can be bound to the antigenor antibody on the solid support, then the solid support is thoroughlywashed and the label (fluorescent, radioactive, chemiluminescent, or thelike) is detected by an appropriate mechanism, and finally the analyteof interest (antigen or antibody) is quantified from the detected label.

Most of today's automated immunoassay analyzers are designed for "walkaway" operation, where the technician loads sample containing tubes ontoa carousel and presses a start button. Thereafter, the automatedimmunoassay analyzer mixes appropriate reagents (often stored aboard theanalyzer) with the sample, performs incubating and washing operations,detects the label, and computes the quantity of analyte in the samplefrom the detected label and stored calibration curves. The entireoperation is typically done under computer control, and in someautomated immunoassay analyzers, bar coding is used to identify thesample under test. The results of the immunoassays are typically outputonto computer paper for inspection by the technician, or they can bemonitored and displayed in real time as described in U.S. Pat. No.5,316,726 to Babson et al. The immunoassay instrument described in U.S.Pat. No. 5,316,726 employs assay tubes that are preloaded with theimmunoassay beads before the tubes are placed on the instrument.

Another automated immunoassay instrument is described in a tradebrochure published by Olympus (Biomedical Products Division),Wendenstrasse 14-16, 2 Hamburg 1, Germany, describing an automatedenzyme immunoassay analyzer under model no. "PK310", which is asequential batch-processing system using a reaction disc containingU-shaped reaction tubes. A bead storage unit is included on-board theinstrument for loading of assay tubes on the instrument comprising aplurality of bead cassettes mounted on a carousel. Each bead cassettestores a plurality of solid support beads as a column on a spiral track,where the beads exit the bottom of the spiral track into an open-airholding receptacle adjoining the outside of the base of the bead pack.The dispensed beads are picked up by a vacuum-operated bead transportfor feeding into a U-shaped reaction tube.

With respect to hospital and clinical laboratories performing largenumbers of tests per month, e.g., at least 5,000 tests per month,immunoassay systems are demanded which can handle high volume LIS basedtest ordering while retaining the capability of accepting test ordersand any prioritizations directly from an operator.

SUMMARY OF THE INVENTION

It is an object of this invention to provide an improved automatedimmunoassay analyzer.

It is another object of the invention to provide a high throughputautomated immunoassay system which can perform high volume testing on abroad range of analytes while selecting from among a diverse set ofimmunoassays.

It is a further object of the invention to provide capacity to perform awide range of different types of immunoassays by storage and automatedcombination aboard the instrument among a wide variety of differenttypes of reagents and immunoassay beads stored on-board the instrument.

It is yet another object to provide an automated design which allowsreduced user interface (e.g., tests are performed automatically fromcomputer input) including the ability to order, perform and reassaytests reflexively based on test results without operator intervention.

It is a another object of the invention to provide an instrument that isnot sample tube specific; that is, an instrument that can accept sampletube sizes within a broad size range.

It is yet another object of the invention to provide a re-useable sampledilution well and a re-useable bead wash station to reduce manual laborrequirements and avoid the waste of single-use disposable mixing cups.

According to the invention, an improved automated immunoassay analyzeris provided. The inventive automated immunoassay analyzer allows forloading and specimen extraction from the original sample tubes loadeddirectly on-board the instrument, wherein a wide variety of differenttypes of tests can be performed on any given sample by the provision ofa bead pack carousel and a reagent carousel that can be computercontrolled to allow automated picking, choosing and combining among thevarious beads and reagents with a sample on-board the instrument toconduct the test(s) desired for each sample. The analyzer has a computercontrol which controls the selection of reagents and beads forperforming a variety of immunoassays on a number of different sampleswhich are loaded into the analyzer. In addition, the computer controlsthe timing of incubation, mixing, washing, and detection operations.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, aspects and advantages will be betterunderstood from the following detailed description of the preferredembodiments of the invention with reference to the drawings, in which:

FIG. 1 is a generalized block diagram of the automated immunoassayanalyzer;

FIG. 2A is a plan view diagram of the flow path of samples and assaysthrough the automated immunoassay analyzer;

FIG. 2B is a partial schematic view diagram of the flow path of samplesand assays through the automated immunoassay analyzer;

FIG. 3 is a flow chart of the processing steps performed on the assaytubes in the automated immunoassay analyzer;

FIG. 4A is a cross-sectional side view of a rack with a sample containerholder of the invention mounted on a carousel;

FIG. 4B is a fragmentary cross-sectional side view of an individualsample container holder sleeve of the invention holding a relativelysmall test tube;

FIG. 4C is a top view of the sample container holder sleeve of FIG. 4B;

FIG. 4D is a fragmentary cross-sectional side view of an individualsample container holder sleeve of the invention holding a relativelylarge test tube;

FIG. 4E is a top view of the sample container holder sleeve of FIG. 4D;

FIG. 4F is a top view of a carousel segment supporting a samplecontainer rack of the invention;

FIG. 5A is a fragmentary cross-sectional side view of a reagentcontainer with re-sealable lid of the invention;

FIG. 5B is a top view of the reagent container with re-sealable lid ofFIG. 5A;

FIG. 5C is a rear view of the reagent container and re-sealable lidalong the direction 5--5 indicated in FIG. 5B;

FIG. 5D is a fragmentary top view of the lid means of the invention;

FIG. 5E is a fragmentary side view along direction 5'--5' of FIG. 5B ofthe of the self-sealing horizontal arm of the lid means and ramp guidemeans system of the present invention;

FIG. 5F is a fragmentary end view of along direction 5"--5" of FIG. 5Bshowing an interlocking ramp guide means and horizontal arm system forthe lid means;

FIG. 5G is a side exterior view of a reagent container with are-sealable lid of the invention in a closed position;

FIG. 5H is a side exterior view of a reagent container with are-sealable lid of the invention in an open position;

The FIG. 6 is a cross-sectional view of a sample dilution well system ofthe invention;

FIG. 7A is a cross-sectional side view of a dispenser device of theinvention;

FIG. 7B is a cross-sectional top view of the bead chamber and itsplunger chamber from the perspective of direction B7--B7 indicated inFIG. 7A;

FIG. 7C is a fragmentary side perspective view of the bead trackcomponent of the dispenser device of FIG. 7A;

FIG. 7D is a fragmentary top perspective view of the plunger componentof the dispenser device of FIG. 7A;

FIG. 7E is a fragmentary side perspective view of the plunger componentof the dispenser device of FIG. 7A;

FIG. 7F is a cross-sectional top view of the bead chamber, bead track,and plunger biasing spring from the perspective of direction C7--C7indicated in FIG. 7A;

FIG. 7G is a cross-sectional side view of a dispenser device of theinvention showing the at rest and dispensing modes of the device;

FIG. 8A is a cross-sectional side view of a tube wash system of theinvention in a nonengaged status with an assay tube;

FIG. 8B is an enlarged fragmentary cross-sectional side view of theassay tube used in the tube wash system of FIG. 8A;

FIG. 8C is a top view of the assay tube of FIG. 8B;

FIG. 8D is an enlarged view of encircled area R in FIG. 8B;

FIG. 8E is a cross-sectional side view of a tube wash system of theinvention in an engaged status with an assay tube;

FIG. 8F is an enlarged bottom view of a drive chuck used in a high speedspinning station of a tube washing station of the invention;

FIG. 8G is a top perspective view of the drive chuck of FIG. 8F; and

FIG. 8H is a top perspective view of a tube holder used to support thebottom of a test tube during its washing in a tube washing station ofthe invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION

The analytical instrument of this invention produces reportable assayresults through the processing of specimens and various other componentsof the chemistry system. This processing involves the control and timingof various internal operations as well as the acquisition and processingof data generated internally or through interaction with an externalcomputer system such as LIS. The analytic instrument is an integratedelectromechanical apparatus which processes specimens in order togenerate test results. It is comprised of all the mechanical hardware,electronic hardware and software required to perform immunoassaysdescribed herein. It is anticipated that many different constituents inthe sample can be tested by immunoassay by the inventive instrumentdepending on the selection of the biomaterial bound to the inert support(e.g., bead) in the assay tube.

Referring now to the drawings, and more particularly to FIG. 1, there isshown a generalized block diagram of the automated immunoassay analyzerwherein the instrument 10, described in greater detail elsewhere herein,that actually performs the immunoassays on multiple samples is connectedto a computer 12 via data communication lines 14. The data communicationlines 14 are used to supply information from the instrument 10 tocomputer 12 such as bar coded information on sample tubes, reagentsupply packs, and bead supply packs on-board the instrument as well asphoton counts measured by a photomultiplier tube. The instrument 10 ispreferably operated under the direction of on-board microprocessors (notshown). The operations and layout of the instrument 10 and computer 12are discussed in more detail in conjunction with FIGS. 2A,B and 3. Thecomputer 12 is connected to a display 16 which presents the operatorwith a status report on all tests ordered and operations occurringwithin the instrument 10. A display 16 is provided to display operatorcommands and data collected from the instrument. A keyboard 18 isprovided for the operator to allow input of patient informationassociated with, and tests desired for, their test samples or to performother analysis and control functions.

FIG. 2A shows the internal details of the instrument 10. The basiclayout and functions of each subsystem of the instrument are summarizedbelow with more detailed descriptions of several of the subsystemsprovided later herein.

A reaction tube feeder/dispenser 201 is a device which accepts reactiontubes 840 (see FIGS. 8A-C) in bulk in a hopper, orients them anddelivers them individually to the reaction tube load chain 202, such asvia an elevator ladder means (not shown). The reaction tubes 840 aredisposable unit dose devices used by the instrument to contain beads andreagents during processing. They serve to contain sample/reagentmixtures during sample pre-treatment operations when required. As such,all transportation, incubation, separation and signal generation stepsfor all tests are carried out in these reaction tubes. The reaction tubeloader chain 202 is a chain having arcuate, horizontally oriented arms202a that accept reaction tubes 840 from the reaction tube dispenser201, supporting the tubes 840 at flanges 846, such as seen in FIG. 8B,integrally formed at the top of the reaction tubes 840. The chain 202transports the reaction tubes 840 first under a tube outlet where beadsdrop by gravity after being dispensed from the bead dispenser andcarousel 203.

The bead carousel 203 supports a plurality of bead packs 203a, 203b,203c, and so forth, each capable of holding a large number of beads andcapable of dispensing a single bead at a time. An individual bead packtypically will contain a single type of bead which is suitable for usewith a variety of different reagents. More than one pack of a given typecan be resident on the instrument simultaneously. This allows forselection among the different types of stored beads. The beads involve abiomaterial used to quantitate analytes in solution that is bound to orpainted upon an inert support body, such as a glass or plastic bead ofabout 5 to 7 mm in diameter. The biomaterial generally is selected froman antigen or an antibody. One bead is consumed for each test conducted,and a particular type of bead may be used for any number of differentassay types. Vertically oriented bar codes can be provided on the outerperiphery of all bead packs which will be accessible for reading by adedicated CCD bar code reader 212 for the bead carousel 203. The entirebead carousel is housed within a dehumidified chamber maintained atabout 10% relative humidity. Again, beads may be dispensed one at a timefrom any pack. Thus, the beads are originally separate from the reactiontubes, not pre-assembled; and the beads thus are selectively added tothe tubes on aboard the instrument 10 depending upon which test isordered for a sample. After a single type of bead is fed to the reactiontube, the chain 202 advances the reaction tube to a position where it isshuttled to the reaction tube pipetting station 204 where reagent and(diluted) sample can be introduced via the reagent pipettor 205 andsample pipettor 206, respectively, to be combined with the dispensedbead at the bottom of the reaction tube 840. Specifically, the reactiontube is pushed into a reaction tube processing side chain 213b of areaction tube processor 213 via a reciprocal plunger to position thereaction tube at reaction tube pipetting station 204.

A rotatable sample carousel 207 accommodates a plurality of easilyremovable tube racks 208, each capable of holding a plurality of sampleor diluent test tubes 208a. Deionized water or a protein diluent can beused as the sample diluent. Vertically oriented bar codes can beprovided on the outer sidewalls of all tubes which are accessible forreading by bar code reader 210 as the carousel 207 rotates. The barcodes on the sample tubes 208a are manually rotated by an operator to beexposed to and read by the bar code reader 210 before operation of theinstrument 10 in the automated mode to inventory the samples andlocations thereof on the sample carousel 207. The bar code reader is ascanning laser bar code reader which can read specimen and diluent barcodes on the sample carousel 207 and reagent bar codes on the reagentcarousel 209.

The individual arcuate sample racks 208 are loaded upon the samplecarousel platform 207a to effectively position the sample tubes 208asuch that their bar codes present an unobstructed optical line to thebar code reader 210. The sample tube holders 208b, e.g., hollow sleeveshaving resiliently-biased tube gripping means, also have a slit in thesleeve wall to expose the bar code on the sample tube. The samplecarousel 207 includes a gap 207b through which the bar code reader 210can scan the reagent carousel 209 located within the sample carousel207.

The sample (and its diluent) pipettor 206 has a downward projectingpipette tip (not shown) positioned at the end of a pipette arm which canbe actuated to travel both vertically (i.e., perpendicular to the planeof the paper) and circularly in arcuate swaths (i.e., along the plane ofthe paper). The amount of Z-axis translation of pipettor 206 is closelycontrolled by a level sensing scheme (not shown) so that the pipettorcan be assured of dipping enough into the sample or diluent to siphon upthe correct amount of fluid, but shallow enough hot to damage theoperations of the of the pipettor 206 or corrupt the pipettor 206 withfluid which may be carried over to the next tube. This pipettor 206 hasan arc of motion which permits it to intersect and travel to and from:(i) the sample tubes and diluent tubes when located at the samplepipetting station 206b on the sample carousel 207, (ii) the sampledilution well 211, (iii) the reaction tube pipetting station 204 wherereagent and (diluted) sample are introduced via the reagent pipettor 205and sample pipettor 206, respectively, and (iv) its probe wash station206a where water can be pumped through the inside of the sample pipette206 to flush out the pipette interior and water also is rinsed over theexterior surfaces of the pipette tip after execution of any or each ofoperations (i), (ii) and/or (iii).

Sample tube elevation sensors 206c preferably can be provided asindicated in FIG. 2A and they can be photoelectric sensors used todetect the height of the sample tube at the sample pipetting station206b. Also at the sample pipetting station 206b, clot detectionoptionally can be performed on the sample by the sample pipette 206using a pressure transducer and an analog-to-digital signal conversionscheme such as those generally known in the field. If the sample failsthe clot detection test, the sample can be defaulted and its testdiscontinued by the computer control.

The sample dilution well 211 is a device, in which a mixing tube is setin rotation, which rapidly mixes quantities of sample, diluent and waterto form a homogenous mixture. These materials are added to the well bythe sample pipettor 206, and mixing is accomplished by agitation of thiswell. In turn, disposal of excess mixture from the dilution well isaccomplished by rotating the well at high speeds.

The reagent carousel 209 is a rotatable carousel which accommodates aplurality of wedge-shaped reagent packs 209a, 209b, 209c, and so forth,each capable of holding a plurality of different reagents in separatecompartments formed in each pack. The immunological reagents are inliquid form and consist of compounds which recognize specific analytescoupled to one of the labels bound to the beads. Three compartmentwedges are shown in FIG. 2A. These packs have self-sealing covers, aswell as vertical bar codes on the outer periphery of the reagent packswhich are accessible for scanning by the sample and diluent bar codereader 210 through sample carousel gap 207b. The entire reagent carousel209 is housed within a stationary refrigerated chamber (not shown)maintained at about 4° C. The chamber will include an sidewall opening,such as filled with a window, on the outer peripheral side of thereagent carousel 209 which permits the bar code reader 210 to read thebar codes presented on the outer peripheral sides of the reagent wedgesas the bar code beam passes through the gap 207b in the sample carousel207 (held stationary during inventory on the reagent carousel) and thewindow on the reagent carousel 209. The reagent chamber housing alsowill have a cover having holes provided which can be aligned withopenings in underlying reagent wedge compartments to permit access bythe reagent pipettor 205 through the reagent chamber cover.

The reagent carousel 209 and sample carousel 207 each has its own rotarydrive so that either can be individually rotated, for example, while theother is held stationary to allow inventory to be taken of eithercarousel, or to sequentially advance sample tubes around the samplecarousel 207 to sample pipetting station 206b during automated assaymode, or to advance reagent wedges around the reagent carousel 209.

A reagent pipettor 205 also has a downward projecting pipette tip (notshown) positioned at the end of a pipette arm which can be actuated totravel both vertically (perpendicular to the plane of the paper) andcircularly in arcuate swaths (along the plane of the paper). This probe205 has access to the reagent carousel 209, a reagent probe wash station205a and reaction tube pipetting station 204 where the reagent iscombined with the bead and sample in a reaction tube 840.

The software of the computer 12 controls the sample pipettor 206 andreagent pipettor 205 to co-ordinate sequential deposits of fluids intothe reaction tube at the reaction tube pipetting station 204. That is,if one pipette is detected as being situated over the reaction tubebeing fed at the reaction tube pipetting station 204, the other pipettewill wait for the other pipette to clear the reaction tube beforeswiveling over the mouth of the reaction tube to deposit itscontribution to the reaction tube.

After introducing the appropriate combination of sample and reagent intothe reaction tube 840 at reagent pipetting station 204, the reactiontube 840 is indexed once, i.e., moved 90 degrees, where it is picked upand advanced by reaction tube processing main chain 213a of the tubeprocessor 213. The reaction tube processor 213 comprises a serpentinechannel 213' having a depth which permits flanges 846 of reaction tubes840 (e.g., see FIG. 8B) to rest on the top of the channel, and mainchain 213a is a top track chain overlying and following the serpentinechannel 213'. Main chain 213a has baffles (projections) (not shown)extending downward to contact and incrementally advance the reactiontubes through the serpentine channel 213'. In this way, the tubeprocessor 213 transports reaction tubes along a serpentine path forincubation of the tube contents and ultimately transfers the tubes backto a side track chain 213b also located within the housing for tubeprocessor 213, which, in turn, conveys the reaction tubes to the washstation 214 or returns reaction tubes to the beginning of the serpentinechannel 213' for supplemental incubation.

The residence time for the reaction tubes in the tube processor 213 fora single pass is about 30 minutes and tube processor 213 is heated to37° C. The side track chain 213b in the tube processor 213 is a trackchain with arcuate arms that support the reaction tubes at flangesintegrally formed at the top of the reaction tubes, similar to chain202.

In one preferred arrangement, a plurality of reciprocating bars are usedas reaction tube shaker bars (not shown), which are located on thebottom of the tube pathways in the tube processor 213 and they areoriented at a direction parallel to the direction of travel of thereaction tubes in the tube processor 213. These shaker bars can bump thebottom portions of the reaction tubes and thereby continuously agitatethe reaction tube contents to promote the immunological reactions.

After leaving the serpentine channel 213', side chain 213b picks up thereaction tube at the end of the serpentine channel 213', and the mainchain 213a circles back to its starting point 90° from reaction tubepipetting station 204, as shown more clearly in FIG. 2B having chainmovement direction arrows provided. If additional incubation is desiredfor a sample, chain 213b is used to circle the reaction tube back to thebeginning of the serpentine channel 213'. On the other hand, if thereaction tube needs to be advanced to wash and photometric analysis, thereaction tubes are shuttled out of the tube processor 213 and are pickedup by a circular chain and moved to a high speed spin wash station 214.The wash station includes an angled, splined chuck surrounded by areceptacle and a tube elevating device (as shown in FIGS. 8A and 8E).Reaction tubes are first elevated onto this chuck and then rotated abouttheir longitudinal (vertical) axes at high speed, whereby tube fluidsclimb up outwardly tapered inside walls of the reaction tubes undercentrifugal forces to expel fluids along the grooved chuck but retainingthe immunoreactive bead within. The waste fiuids drain into the liquidwaste receptacle. Washing is accomplished by the addition of water intothe tube one or more times to the tube during, or followed by, highspeed centrifugation.

After washing the beads at the wash station 214 and expelling fluidcontents of the reaction tube, the reaction tubes are either: (i)shuttled out of the wash station onto a luminometer chain 215a of adetection station 215 where a substrate is added and quantification madeof the analyte of interest, or (ii) returned to reaction pipettingstation 204 by side chain 213b where more reagent(s) is added, ifnecessary for the assay, before the steps of incubation and wash arerepeated. The luminometer chain 215a transports the reaction tubes fromthe wash station 214 to a photo-multiplier tube (PMT) 216a at a reactiontube reading station 216 of detection station 215 for photometricreading, and then the chain 215a moves the assayed tube and its contentsto waste. In the detection station 215, the luminometer chain 215a is aside link chain including lower reciprocating shaker bars, similar tothose used in the tube processor 213, and the detection station 215includes an incubator and luminometer block heaters for heating the tubecontents after addition of substrate.

In the preferred embodiment, chemiluminescent techniques are used toquantify the analyte. Signal generating chemistries for chemiluminescenttechniques include one of either of two formats, each of which causeemission of light from the surface of the processed analytical elements(beads) to produce varying light intensities in response to theconcentration of a sample analyte to be quantified. These two differentchemistries require the following signal generating reagents storedaboard the instrument 10: chemiluminescent enzyme substrate stored inreservoir 215b for the first chemistry, and first and second triggerreagents stored in reservoirs 218a and 218b for the second type ofchemistry. Thus, depending on the chemistry employed by a particularbead, appropriate signal reagents will be added to its reaction tube.For instance, the three signal reagents can be used with each beingpumped by a separate, independently controlled solenoid pump at pumpingstation 220. Each pump is connected to one of three spigots (not shown)which reside over various sites on the luminometer chain 215a.

In the first chemiluminescent technique, alkaline phosphatase substrateis used. Where the bead employs the alkaline phosphatase label, it willreceive chemiluminescent substrate in the first luminometer chainposition proximal to the tube wash station 214.

The second type of test involves use of acridinium ester with injectionof trigger reagents into the reaction tube at the reading station 216and making an unattenuated count.

Of these two chemistries, it is preferred to label the assay specificantigen or antibody in the reagent with alkaline phosphatase which willcleave a phosphate ester stabilized dioxetane. Decomposition of thedioxetane results in the emission of light photons which can bequantified at detection station 215 and are proportional to the quantityof analyte present. The light signal emitted from the bound labeledanalyte on the inert support bead in the reaction tube is measured andthe quantity or analyte determined by the computer 12 by reference to anappropriate standard curve. However, it should be understood that otherdetection schemes such as fluorescence or radioactive ion emission couldbe used and appropriate labeling of reagent is required.

The reaction tube, as containing the washed bead and substrate solution(e.g., chemiluminescent alkaline phosphatase substrate), is incubated onthe luminometer chain 215a for about 5 minutes at 37° C. and advanced toa position in front of the photomultiplier tube 216a where photon countsare measured.

The PMT 216a is part of the reaction tube reading station 216 which alsoincludes a luminometer shutter and attenuator wheel of the types asdisclosed in U.S. Pat. No. 5,316,726, which description is incorporatedherein by reference. Again, the reaction tube reading station 215employs the PMT 216a to take light emission measurements on reactiontubes as they pass. A shutter (not shown) is employed to preventcrosstalk between adjacent tubes at the PMT station. This shutter devicephysically isolates the tube at the PMT 216a from those surrounding it.A rotatable filter (attenuator) wheel (not shown) is mounted between thePMT 216a and the reaction tube position in reaction tube reading station216 when being read for photon counts. This wheel has three positions:dark (PMT 216a receives no light), unattenuated (PMT 216a receives fulllight output of the reaction tube); and attenuated (a neutral densityfilter that is positioned between the PMT 216a and reaction tube to makeattenuated counts). The features of such shutters and filter wheels arefully explained in U.S. Pat. No. 5,316,726. For example, a filter wheelcan have three sections; an open section for making unattenuated counts;one or more neutral density filter sections for making attenuatedcounts; and an opaque section for making dark count measurements tocalibrate "noise" in the PMT 216a. Photometric data can be gathered bymeasuring the PMT dark counts and taking an attenuated count (known asthe precount), and determining whether the precount value is above orbelow a preset cutoff value to determine whether an unattenuatedmeasurement may be needed if the precount is below a cutoff value.

The average photon counts per second are converted to analyteconcentration by the computer 12 using standard curves whichmathematically relate photon counts to concentration. The photon countand concentration information for each reaction tube is archived to amagnetic storage device for later analysis. The concentration for thereaction tube is also sent to display 16 of the computer 12. Periodiccalibration with known calibrating solutions maintains the mathematicalrelationship for a particular instrument 10 and lot of reagents.Calibration of the standard curves may be performed according toprotocol such as described in U.S. Pat. No. 5,316,726, which descriptionis incorporated herein by reference.

Fluidic systems are provided throughout the instrument 10 as system ofpumps, valves, tubing and reservoirs adequate to provide for thetransfer and disposal of fluids, as needed, throughout the instrument.Among these, the pumps include several positive displacement pumps 217a,217b used in conjunction with the reagent and sample pipettes to permitwithdrawing and feeding of precise amounts of sample and reagent. Thesubstrate reservoir 215b stores the chemiluminescent substrate which ispumped via injector pump 219 to the first chain position on luminometerchain 215a at detection station 215 via tubing lines (not shown). Liquidwaste drained from the dilution well 211, wash station 214 are collectedon-board the instrument 10 in a liquid waste reservoir stored aboard theinstrument 10 for appropriate disposal, and the reaction tube and itscontents including the bead and any liquid are collected from detectionstation 215 after completion of the photon count in a solid wastereservoir aboard the instrument 10 for appropriate disposal. Othersupporting fluid management equipment such as tubing lines, and soforth, is not shown for sake of simplifying the illustration.

The computer control 12 allows the operator to pick the tests desiredfor each sample, and, if desired, to prioritize the sample if stat orunstable. A technician informs the computer 12 via keyboard input orother input means of the relevant patient information and tests desiredfor each sample before placement of the sample's tube on the samplecarousel 207, and the location of the sample tube can then be tracked onthe sample carousel 207 by the sample tube's bar code. Similarly, thecontents of each reagent wedge and bead pack are loaded into thecomputer's memory and their locations then can be tracked about theirrespective carousels by their bar codes. The computer 12 can theninstruct the instrument 10 to pick the right bead and right reagent andput them in a reaction tube with a particular sample for assay. A systemof logic circuitry, cabling, user input/output devices and software isprovided for computer 12 which accepts user commands and displays theresults of those commands. Devices directly accessible to the user formanaging the computer 12 can include a high resolution color monitor,keyboard, trackball, floppy disk drive, CD-ROM drive and speaker. A VDTcan be included for computer 12 that tracks the location and status ofeach sample (e.g., untested/test underway/ tested) intermittently, e.g.,about every 18 seconds.

In preparing the instrument 10 for use, an operator first loads allrequired bulk materials into appropriate on-board storage areasincluding the reaction tubes, bead packs, reagent packs, bulk fluidsincluding water, probe wash and bead wash solutions, and signal reagentsincluding substrate and trigger reagents. Liquid and solid wastecontainers should be checked to see if they need emptying. A work listis created either manually of through LIS download. The sample, diluent,and any control or adjustor containing test tubes are loaded onto thesample racks that are placed on the tube carousel, and all tubes aremanually rotated so that their bar codes face outwards. Samples whichrequire a known dilution are identified in advance, any samplesrequiring STAT priority handling are identified.

Inventory is automatically conducted on the test tubes in the samplerack, the reagent packs on the reagent carousel, and on the bead packson the bead pack carousel, by rotating each respective carousel by itsrespective bar code reader to interrogate the contents aboard each ofthe sample, reagent and bead back carousels, and the information fromthe bar code reader is sent to the computer 12 which tracks the positionof all sample tubes 208a, reagent pack 209a, 209b, 209c, and so forth,and bead packs 203a, 203b, 203c, and so forth, within the instrument 10.Not all spaces on each carousel need by filled since the bar codereaders will simply identify an empty space on any of the samplecarousel, reagent carousel, or bead pack carousel, to the computer 12,and the computer will track the empty space. Position information can bederived and tracked with use of a shaft encoder (not shown) provided onthe motor drive to counts steps of the motor such that the position ofeach sample tube, reagent pack, and bead pack is known by the instrument10. In conjunction therewith, an internal optical sensor (not shown)formed of an emitter and detector pairing can be built into eachcarousel to reacquire and recognize, each time the instrument is startedup, a fixed metallic reference point or "flag" in the device provided asa home or reference point from which motor steps can be counted fromwhich to get to any position. In this way, the steps of the motor neededto move a sample tube to the sample pipetting station, or a reagent ordiluent to the reagent pipetting station, or a bead pack to the beaddispensing position, can be managed by the instrument 10. Samples,reagents or bead packs can be replaced as needed during instrumentoperation.

After any interruption of the operation of the instrument, inventory isautomatically taken again of the various sample rack, reagent pack, andbead pack carousels before testing is resumed. For example, whenever apause command is hit by the operator at the computer control, or a sealis disrupted in the system, e.g., by opening the housing on the reagentcarousel or bead carousel, the instrument 10, when put back on-line,first re-inventories each of the bead carousel, reagent carousel, andsample carousel with the bar code readers to learn any changes possiblymade. In this way, the location of each sample tube, or absence thereof(an empty space on the sample carousel 207a), is known by the system,and the reagent and bead packs present on the system are also known.This allows the computer to know what and where things are on theinstrument. The sample tubes are then assayed methodically in sequencearound the carousel unless prioritization, e.g., for STAT or unstablesamples, has been requested at the computer control by the operator.

FIG. 3 illustrates the basic process steps performed by the instrument10 of the automated immunoassay analyzer. First, at step 310, the sample(and any diluent tubes) are loaded into sample tube holder racks whichare positioned on the sample carousel. Second, at step 312, the contentsand carousel location of each the sample tubes, reagent packs, and beadpacks are determined by bar code readers. At step 314, a portion ofsample is withdrawn from a sample tube and mixed with diluent in thedilution well to form a homogenous mixture. The dilute sample is thencombined with reagent and a bead at the reaction tube pipetting stationin step 316. At step 318, the reaction tubes in which sample and reagenthave been combined with a bead are incubated. The time of incubation isdetermined by the dimensions of the incubation processor and time forincremental advancements in the analyzer. At step 320, the reactiontubes which have been incubated for the requisite period of time aretransferred to a high speed washing station. Washing is achieved byrotating the reaction tubes about their longitudinal axes and bypipetting each water into the reaction tubes. High speed rotation of thetubes causes wash fluid to be rapidly removed from the inert supportcarrying the bound biomaterial which has the bound reagent label. Aftercompleting washing in step 320, the reaction tube and inert bead supportare free of unbound labeled reagent so that only bound labeled reagentwill be detected. At step 322, a chemiluminescent substrate (e.g.,phosphate ester dioxetane) is added to the assay tube, and the reactiontube is again incubated for a short time. During incubation, alkalinephosphatase from the reagent which is bound to the inert support cleavesthe phosphate ester of the chemiluminescent substrate. Decomposition ofthe dioxetane releases photon energy; the emitted light photons areproportional to the quantity of analyte present. After decomposition ofthe dioxetane, the photon emissions are counted at step 324 by aphotomultiplier tube (PMT). At step 326, photon count information issent to the computer for quantitative determination of the analyte.

While a sandwich type assay has been exemplified herein, the instrument10 is amenable to different immunological chemistries for processing bythe system, including any of the formats of sandwich assays, competitionassays, or liquid phase capture assays. The system will support manydifferent test categories, such as thyroid function, sex hormones,growth hormones, tumor markers, infectious diseases, allergy testing,immunoglobulin and related proteins and peptides, steroids and othersmall molecules, therapeutic drugs, drugs of abuse, and vitamins. Thesystem will analyze samples of serum, plasma, or urine, and specificchemistry kits may also handle clarified cerebrospinal fluid or saliva.

The manner of handling certain conceivable errors in the practice of theassay on the inventive instrument is as follows. If there is a lack ofrequired information, such as unreadable bar codes or the absence ofinformation about which tests to run or how to run them, the analyzercan be programmed to verify the availability of all required informationwhenever the specimen carousel is accessed. If any information is foundlacking, the operator can be alerted immediately by audible alarm or viaon-screen display. As such, operators can expect the analyzer to processall on-board specimens before requiring further attention. Also,sample-specific fluidics problems could be encountered. These errorscould involve insufficient sample or the presence of a clot in thesample. Operators can be alerted immediately of such problems via bothon-screen and audible alarms. However, the analyzer will continue toprocess other specimens while awaiting operator intervention. If thereare hardware problems, such as fluidic component failures, clogged inletfilters, and so forth, operators can be alerted immediately of such viaboth on-screen and audible alarms. Until an operator intervenes,sampling operations should be suspended, but tube processor operationscan continue.

More detailed descriptions of the sample tube holding system, bead pack,reagent pack, wash station and dilution well subsystems of instrument 10are provided hereinafter to further illuminate the specific manner ofoperation of the instrument's components.

An improved sample container rack is provided in the inventiveinstrument. Referring to FIG. 4A, there is a sample container rack 400including a base or support platform 401 and an upright cylindricalsample container holder sleeve 402 integral with the base 401. The rackcan include a plurality of such sample container holder sleeves, butonly one representative sleeve is depicted in FIG. 4A for illustrativepurposes. The rack and its holder sleeves can be formed by injectionmolding of plastic. Sample container holder sleeve 402 is acylindrical-shaped shell having a mouth or opening 418 at its upper endand also has a vertically extending slot (not shown) provided in thesidewall 403 of the sleeve, whereby a sample container 404a or 404b(superimposed in FIG. 4A for illustrative purposes only) can be manuallyrotated within the sleeve 403 until an identifying means (not shown),such as a bar code, is visible and readable through the slot. The samplecontainer holder sleeve 402 also includes a plurality of samplecontainer gripping means 405 (with only one representative gripper meansdepicted in FIG. 4A to facilitate the illustration), preferably spacedequidistantly around a circumference of the sleeve (other than at theslot region). Each gripping means 405 has at least one projection tab406 that is resiliently urged inward through an aperture 412 provide inthe holder sleeve sidewall 403 by virtue a spring-like means 407 mountedon the exterior of sleeve sidewall 403 to cause the projection tab 406to be urged against a sidewall portion 408 of the sample container 404aor 404b to center the sample container 404a or 404b within the sleevewell 409 and maintain the sample container 404a or 404b in an uprightorientation. The projection tab 406 can be formed of a rigid, semirigid,or elastomeric material, and preferably is a semirigid elastomericmaterial, such as rubber, having a spring arm 413 embedded therein.Preferably three or more gripping means 405 are located equidistantlyaround a circumference of the holder sleeve 402. In one preferred modeof the invention, three gripping means 405 are equidistantly spacedaround a circumference of the sleeve 402, where each gripping means 405has a pair of projection tabs 406 that are aligned vertically and theprojections are urged simultaneously against a side wall of the samplecontainer. As the sample container is grabbed simultaneously andsymmetrically from all sides during its insertion into the sleeve well409 by the plurality of such gripping means 405, centering of the samplecontainer will be assured. Also, abutment posts 410 can be arranged onthe base 411 of the holder sleeve 402 to further facilitate centering ofthe sample containers 404a or 404b about the central longitudinal axis zof the sleeve 402. The sample container rack 401 can be positioned onand supported on a rotatable carousel aboard an immunoassay analyzer, sothat the various sample containers, as held in centered manner in theholder sleeves, can be transmitted to a pipetting station on theinstrument.

Referring now to FIG. 4B, there is an isolated depiction of individualsample container holder sleeve of the invention holding a relativelysmall diameter test tube 408. FIG. 4C is a top view of the sleeve holderof FIG. 4B indicating the presence and locations of three gripper means405 equidistantly spaced around a circumference of the holder sleeve 402to simultaneously and symmetrically grip the sample container 408 fromdifferent sides. The elements labeled in FIG. 4B and FIG. 4C have thesame meaning as described herein relative to FIG. 4A.

Referring now to FIG. 4D, there is an isolated depiction of individualsample container holder sleeve of the invention holding a relativelylarge diameter test tube 408. FIG. 4E is a top view of the holder sleeveof FIG. 4D indicating the presence and locations of three gripper means405 equidistantly spaced around a circumference of the holder sleeve 402to simultaneously and symmetrically grip the sample container 408 fromdifferent sides. The elements labeled in FIG. 4D and FIG. 4E have thesame meaning as described herein relative to FIG. 4A.

In FIG. 4F, an arcuate tube holding rack 400 is shown in top view thatcan be supported on a portion of an underlying arcuate carousel platform400' aboard an immunoassay instrument. The sample carousel 400'. Therack 400 is an integral object that can be moved at the will of theoperator to any available desired location on such a carousel, spacepermitting. The rack 400 is shown as capable of supporting 15 tubes forexemplification purposes. If more than one rack is used, the variousracks can have an outer profile that is the same geometry, or can differfrom each other, without limitation. The size of the rack and number ofholder sleeves provided on each rack is not particular limited otherthan by the spatial limitations of the carousel 400', as to the rackconfiguration, and of the rack, in terms of the number and arrangementof holder sleeves it has room to support.

The sample container rack of the invention allows the sample containers,as received, including sample containers received in nonuniform sizes,to be loaded directly into an automated analyzer without the need todevote time and effort to assessing the size of the original samplecontainer or transferring the sample contents into a prescribed size ofsample tube. Also, the sample container rack of the inventionautomatically centers the sample container for pipetting operationsregardless of the size of the sample container for a wide range of testtube sizes.

To remove aliquots of sample from a sample container held in a holder ofthe inventive rack, a downward projecting pipette (not shown) can bepositioned at the free end of a translatable pipetting arm. To performpipetting operations, the pipette tip must be inserted into and out ofthe sample tubes (and reagent containers) by moving the pipetting armvertically down and then back up, respectively. The amount of verticaltranslation of the pipetting arm is closely controlled by a levelsensing scheme (not shown) so that the pipetter can be assured ofdipping into a sample container (or reagent container on a reagentcarousel) far enough to siphon up the correct amount of sample orreagent, but shallow enough not to damage the operations of thepipetting station or corrupt the pipetter with sample or reagent whichmay be carried over to the next assay tube. A pair of precision syringepumps can be connected to the pipetting station, where, preferably, oneof the syringe pumps is calibrated for large volumes while the other iscalibrated for small volumes. A probe wash station can be providedhaving separate wash wells for simultaneously flushing the inside andoutside of the pipette tip. Extensive probe flushing on every pipettingcycle eliminates detectable sample carryover. The probe wash stationshould also have a fresh water supply. In a preferred embodiment, thepipetter may pick up one or more small air bubbles separated by water toaid in transfer of sample and reagent to an assay tube.

In usage of the sample container rack system of the invention, anoperator manually uncaps and loads specimens in the sample containers,as received, or a different sample container, if desired, into thesleeve racks arranged on the carousel. By way of example only, and notlimitation, the following types sample containers can be supported bythe rack system of the invention: a) primary blood collection tubes suchas in the following sizes: 12×75 mm; 12×100 mm; 13×75 mm; 13×100 mm;16×75 mm; and 16×100 mm; b) test tubes such as in the following sizes:12×75 mm; 12×100 mm; 13×75 mm; 13×100 mm; 16×75 mm; and 16×100 mm; andc) tube-top sample cups.

The vessels are inserted manually into racks of the invention which canaccept a wide range of specimen containers. The vessels are thenmanually rotated until their bar codes are visible through slotsprovided in each rack, and the rack is installed onto the samplecarousel. Each rack can accept up to 15 specimens or more, and aplurality of racks, such as a total of up to six racks or more, mayreside on the sample carousel at any time, depending on the relativesizing of the racks and carousel. As such, a total of up to 90 or evenmore specimens may be simultaneously resident on the analyzer using therack system of the present invention. An operator may remove a rack fromthe analyzer at any time to supplement or replace the supply ofspecimens. For tracking purposes, each rack position should bedesignated, for example, as position A, B, and so forth, in both humanand instrument readable forms. This information will be readily visiblewhile looking at the sample rack carousel, and, preferably, will also bedisplayed graphically on a computer display screen. The display screencan also be programmed to include other details about specimen samplingin the software description documents, including, for example, whichracks are present on the instrument; the location of these racks inrelation to each other; the location on these racks of specimens anddiluents; the locations of specimens which have been processed are thusno longer needed; the locations of specimens which cannot be used due tosome error condition; and the operating status (whether racks may beaccessed by the operator).

The analyzer instrument can be provided with means to identify specimenseither automatically via bar code or through operator input. In theformer case, specimens will be identified by an accession number orother unique identification imprinted on a label in bar code format. Toallow automated identification, the operator will need to first attachthis label along a linear axis of the specimen tube and then insert thetube into a rack such that the label is visible. An on-board bar codereader can then be used to automatically associate the specimen with itslocation in a given rack. If bar codes are not available, the operatormay install specimens into racks and then inform the computer controlsof the analyzer of the appropriate accession numbers via keyboard and/orpointing device input.

Once specimens have been loaded in the sample container racks, andidentified, the sampling process will entail the following steps:

a) rotation of the sample carousel to position the selected specimen atthe sampling position

b) identification of the specimen tube size

c) positioning of the sample probe at the specimen surface via leveldetection

d) withdrawal of an appropriate aliquot (e.g., about 5 to 100 μL)

e) detection of probe clogging due to particulates or clots in thespecimen

f) detection of other fluidic problems which might invalidate thecurrent test

g) transfer of the aliquot to either a reaction tube or a sampledilution well as required

h) washing of the sample probe in preparation for processing of the nextspecimen.

Operators may specify the order in which samples are processed. STATspecimens will always be processed first, while remaining samples may behandled in any of the following orders: a) sort by rack and by positionwithin rack (default); b) process user designated priority tests first;c) sort by specimen accession number; or d) sort by test type.

In one mode of usage, the automated analyzer using the sample containerrack of the invention is programmed to prompt the operator to select aprimary or secondary default tube type. In the former case, the tubelength will determine the maximum depth at which the specimen surfaceshould be located. If the fluid surface is not detected at or above thislevel, sampling of the specimen will be aborted. This will preventcontamination of the probe by either solids or RBC separation gel in thespecimen tube. Where secondary is the chosen default tube type, theprobe will travel all the way to the tube bottom in search of a fluidsurface. Operators will be allowed to designate individual tubes asprimary or secondary.

Also, it may be desirable to dilute specimens prior to assay at therequest of the operator or automatically. This is accomplished viamixing of a specimen aliquot, water and quantity of a concentrateddiluent in the sample dilution well described herein. Diluents, if sodesired, can be supplied in screw-cap tubes accepted by the on-boardspecimen racks.

In another subsystem of the inventive instrument, there is a uniquereagent container device utilized that is a multi-compartmented vesselhaving reagent contents thereof accessible via a self-sealing lid meansthat functions according to a "living hinge" principle, such that thelid means is biased to provide automatic selfsealing action such thatthe lid reseals access holes of the multi-compartmented vessel once areagent extraction device clears the access holes of the vesselcompartment openings and openings provided in the lid.

Referring FIG. 5A, there is shown a reagent container 500 of theinvention with its self-sealing lid mechanism 503 attached thereto. Thecontainer 500 itself has a reagent vessel 501 comprised of a pluralityof separate reagent storing compartments or wells, indicated as threecompartments in this example of 501a, 501b, and 501c. These compartmentsshare a common cover 514, which provides compartment openings 508a,508b, and 508c, respectively. The openings 508a-c have a size adequateto permit a reagent extracting pipette (not shown) to be introduced intoand retracted from the compartment in an unencumbered manner. Thereagent container can have any convenient geometric shape. The reagentcontainer 500 preferably is provided in an overall wedge-like shape, asindicated in the top view of FIG. 5A, which allows a plurality of suchreagent "wedges" to be situated side-by-side in a pie-like configurationon a carousel, thereby permitting a wide variety of reagents types to beaccessible for immunoassay operations. Alternatively, the reagentcompartments can be positioned in a linear array to provide a box-shapedreagent container.

The reagent vessel 501 can be prepackaged with its compartmentspre-filled with selected reagents deposited in the various compartments.The openings can be optionally pre-sealed with a detachableadhesive-coated metallic foil. The reagent container can be loaded on areagent carousel; sealing foil removed (if any); and then lid means 503attached to the exterior of vessel 501, in a manner described in greaterdetail below.

An important aspect of the invention resides in the self-sealing lidmeans 503 which automatically reseals the reagent container 500 betweenany intermittent reagent extractions from the container without the needfor external force to be applied to effect re-closure. The lid means 503is a molded plastic member with spring-like biasing force generated by abend 516 located below the hinge 507 that compels the lid means torelease any bias force by movement of the horizontal arm 506 along thex-direction towards projection 510 until caps 509a-c cover openings508a-c to move lid means 503 (back) to a "closed" position (see FIG.5G).

When external force is supplied to projection 510 in the x-directionadequate to overcome the normal bias force acting in the oppositedirection, the arm 506 displaces rearward in the direction of hinge 507until caps 509a-c are pushed far enough to horizontally clear theunderlying compartment openings 508a-c. As can be more easily seen inFIG. 5D, the lid caps 509a-c alternate with openings 515a-c. Dependingon the location of arm 506, either the caps 509a-c or openings 515a-ccan be aligned with the underlying openings 508a-c in the cover 514 ofthe reagent vessels. The caps 509a-c are sized slightly larger indiameter than openings 508a-c, respectively, such that the caps coverthe openings when the lid means is in its normal position, versus itsactive position (described in greater detail below). As best seen inFIG. 5D, a second hinge 513 is also provided at a location approximatelymidway between opening 515a and hinge 507. Hinges 507 and 513 can beformed as thinned portions in the lid means 503 during molding. Thehinges 507 and 513 extend side edge-to-side edge and run perpendicularto the major length direction of lid means 503. The first hinge 507allows the arm 506 to generally slide forwards and backwards. The secondhinge 513 relieves stress created in the arm 506 when it is pushedbackwards while traversing and restrained by the ramp guide means 551a,551b (FIG. 5E) such that the arm 506 can retract along a horizontal linewithout tending to significantly arc (see FIG. 5H). Both hinges 507 and513 are formed as thinned plastic regions in the arm molding which formflexure points along the arm 511 and arm 506, respectively. However, thethickness of the hinge must left sufficiently thick to prevent failureof the crimped or thinned hinge-like portion after only limited numbersof flexures.

The lid means 503 also is attached to the side wall 512 of reagentvessel 501 at its lower end. The lid means 503 can be preassembled withthe reagent vessel or attached on site when used. For example, when afresh reagent wedge 500 is provided to a carousel of an immunoassayanalyzer, the protective foil can be stripped from the upper surfaces ofopenings 508a-c to expose openings 508a-c, and the lid means 503 can beattached to the container before or after these steps.

Another aspect of the reagent container sealing system 503 of thisinvention is that the alternating caps 509a-c and openings 515a-c in thehorizontal arm 506 of the lid means 503 are maintained in translationalalignment over the underlying openings 508a-c of the reagent vesselcompartments by use of guide means (not shown in FIG. 5A for sake ofclarity as to other above-discussed features) to restrict sidewaysmovement of the horizontal arm 506 during its movement over the uppersurface of cover 514.

As seen in FIG. SE, ramp guide means 551a and 551b are provided on theupper surface of cover 514. Some features of the lid means and reagentvessel, not essential to understanding this aspect of the invention,have been omitted from FIG. 5E to clarify the illustration. The ramps551a and 551b, and corresponding lid projections 552a and 552b, areinclined at the same relatively small acute angle a relative to thehorizontal plane P extending coplanar with the upper flat surfaceportion of cover 514, such as inclined from the horizontal direction(i.e., the x-direction) at angle ranging from about 5° to 15°,preferably about 10°. The direction of inclination of the ramp guidemeans 551a, 551b steeps up from the front F of cover 514 towards therear RR of cover 514.

The acute angle a established for ramps 551a and 551b (and projections552a and 552b) must be large enough such that as soon as lid means 503is pushed rightward along the x-direction via force applied atprojection 510 (in the perspective of FIG. 5), that the caps 509a-c oflid means 503 are contemporaneously translated upward up the ramps 551aand 551b and out of contact with the surfaces of the cap openings 508a-cof the cover 514. Thus, sliding friction between the cover 514 and lidmeans 503 is avoided without resorting to a loose interfit of lid 503and cover 514. On the other hand, the acute angle a of the ramps 551aand 551bmust be not be set too large so as to make access difficult toopenings 509a-c of cover 514 when lid means 503 is pushed rightwardalong the x-direction via force applied at projection 510. That is, withan ever steeper angle for ramps 551a and 551b, the horizontal profile ofopenings 515a-c in the lid 503 is diminished.

The ratio of the vertical height H of the ramps 551a, 551b, relative tooverall gap T between arm 506 and cover 514, that is, the ratio H/T, isabout 40-50% for the highest point of each ramp and about 5.15% at thelowest end of each ramp. The arm 506, when horizontally displaced overthe upper surface of cover 514, is mechanically guided by ramp means551a, 551b via downward projections 552a, 552b on arm 505 having meansto interconnect with the ramp means 551a, 551b while permittinginter-sliding movement along a single line of direction. For example, asshown in FIG. 5F, interlockable hooks can be integrally formed on theends of projections 552a, 552b and ramps 551a and 551b to allow slidableinterfitting of these components. In more detail, projection 552aactually is comprised of a pair of projections 152a and 152b located onopposite sides of the related cap 509a on arm 506. Similarly, ramp guidemeans 551a, is actually comprised of a pair of upstanding members 151aand 151b extending from cover 514 on either side of cover opening 508a.Projection 152b, like its companion projection 152a, terminates in adownward projecting hook 521 which mechanically interfits with anupstanding hook or rail 511 formed in ramp guide portion 151b.

Therefore, an important aspect of the invention is that when force isapplied to projection 510 in the x-direction by an operator orelectromechanical actuator, the projections 552a and 552b will slide upramp guide means 551a and 551b, respectively, avoiding sliding frictionwithout resorting to loose interfit between the lid 503 and cover 514.Preferably, when access to the reagent compartments is desired,projection 510 is horizontally pushed with adequate force to overcomethe normal opposing bias force in the lid means 503 caused by spring-arm511 until caps 509a-c in the arm 506 clear compartment openings 508a-cand openings 515a-c instead align over the compartment openings 508a-c.

The lower end of arm 511 of lid means 503 can be attached to thesidewall 512 of the reagent vessel by any convenient means. As onetechnique to attach the arm 511 of lid means 503 to the inner verticalsidewall 512 of the reagent container 500, as shown in FIG. 5C, theinner vertical wall 512 of the reagent vessel 501 can have a sleeve 505comprised of two upstanding walls 505a and 505b, which define an openingsized to receive tongue member 504 of arm 511 of lid 503, and a coverside 505c (see FIG. 1) integral with side walls 505a, 505b whichprevents movement of the arm off the sidewall 512. The tongue member 504has a pair of prongs 504a and 504b that are normally biased outward inthe y-direction, but which can be displaced inward in the y-direction byoperator handling.

FIG. 5D is a fragmentary view of the lid means 503 alone, where thelabeled elements have the descriptions set forth herein. The prongs 504aand 504b of tongue 504 of the lid means, are inserted into the sleeve505 through opening 513 to grip the respective walls 505a and 505b dueto the outward spring-like bias of the prongs 504a and 504b, to attachthe lid means 503 to the reagent vessel 501. Ribs or flanges (not shown)also can be formed on the inner sides of walls 505a and 505b of sleeve505 to mechanically enhance the interlock between the tongue 504 andsleeve 505.

The reagent wedges, i.e., "reagent packs", of the invention willsimultaneously support a relatively large number of assay types, e.g.,up to 24 or more, each requiring up to 3 or even more liquid reagents,without reduction of the on-board assay capacity of an automatedchemical/biochemical analyzer. The reagent packs of the invention alsoprovide the ability to store and preserve reagents on-board animmunoanalyzer, for example, for relatively extended periods of time,e.g. one month, without detectable degradation. The reagent packs of theinvention also permit reagents to be positively identified via anattached bar code.

A rotating carousel described herein accommodates a plurality ofwedge-shaped reagent packs, each reagent pack capable of holding aplurality of different reagents in different compartments thereof. Thesepacks include instrument actuated covers as well as vertical bar codeswhich are accessible to the specimen and diluent bar code reader. Theentire carousel is housed within a refrigerator chamber maintained atabout 4° C.

By way of illustration, in immunoassay analysis, the reagents aresupplied in liquid form, and are used to generate a detectable signalproportional or inversely proportional to the concentration of analytein a specimen. During processing, they are deposited into individualreaction tubes associated with a bead having an appropriate biomaterialcoated on its surface for the test needed on the sample. Reagents arecontained within disposable packs, each bearing a plurality, e.g., up tothree or more, different reagents in separate respective compartments.These packs protect their contents from the environment by virtue oftheir instrument actuated lids and their construction from coloredtransparent materials. The packs are also constructed of a material,such as plastic, that is sufficiently translucent to permit operators tovisually observe from the outside the fluid levels within.

A plurality, e.g., up to 24 or more, of different reagent packs can besimultaneously resident on the analyzer instrument, and the operator mayreplace or supplement the supply of packs at any time. A quantity ofreagent may be consumed from one or more of the chambers of a reagentpack for each test conducted. A particular reagent pack may be used forseveral different test types, but reagent/bead lot matching is requiredfor each test type the reagent pack supports. A given test must usereagents from one and only type of reagent pack. More than one pack of agiven type may be resident on the analyzer instrument simultaneously.Reagent packs serve the following functions:

a) to protect the reagents they contain from evaporation;

b) to protect the reagents they contain from contamination;

c) to package the reagents in a manner convenient for operator accessand handling;

d) to facilitate the dispensing of reagents into each reaction tube asneeded;

e) to provide the necessary space for attachment of labeling; and

f) to enable visual estimation of reagent inventory by the operator.Reagent packs can be bar code labeled with all the information needed toidentify them to both an analyzer instrument and the operator.

A high performance sample dilution system is also provided in theinventive instrument. In the sample dilution system of this invention,there is a unique combination including a dilution well waste chamber, adilution well spinning means located in the base of the chamber, and are-useable dilution well removably nested in the spinning means that isused to mix and dilute liquid samples by rotary motion imparted by thespinning means.

Referring to FIG. 6, there generally is shown a sample dilution system610 of the present invention. Specimens may be diluted prior to assayeither at the request of the user or automatically. This is accomplishedvia mixing of a specimen aliquot and a quantity of a diluent, such as aprotein diluent or deionized water, in the sample dilution system 610.The dilution well waste chamber 611 is an enclosure defined by chamberwalls 620 of chamber body 615 and a removable dilution well cover 613.As illustrated, the waste chamber 611 can be conveniently formed atleast partly recessed in a work station table top 612, such as of animmunoassay instrument. The removable dilution well cover 613 has acentral opening 614 for pipette access. Concentric projections 614' and614" extending from the lower side 613' of the cover 613 help direct apipette into the mouth 631 of the dilution well 625 and channel wastefluids during well cleaning, respectively. The chamber body 615 includesflange 617 retaining O-ring 616 which forms a seal with the rim 618 ofthe cover 613.

The chamber body 615 is stationary and defines inner sidewalls 620, andbottom 621 having a drainage port 636 and a centrally located opening619. The central opening 619 houses a rotatable dilution well spindle622. Bearings 624 are provided between the stationary chamber body 615and the rotatable spindle means 622. The spindle 622 includes a hollowsleeve 622' defining a recess 623 sized to allow the dilution well 625to be nested and frictionally interfit inside the spindle 622 such thatthe dilution well 625 will travel in rotation with the spindle 622. Thespindle can be driven in rotation by adjustable motor 628 having driveshaft 629 mechanically connected to spindle 622 via a coupling 630.Teflon seals 626 are also preferably provided between the chamber body615 and spindle 622, as shown, to provide a water-tight system thatseals the bearings 624 and motor 628/drive 629 from contact with fluids.The rotatable spindle 622 can be stainless steel or another materialthat is corrosion resistant in the presence of water.

The dilution well 625, shown as a test tube-like insert configuration inthe FIG., is nested in the rotatable spindle 622 during a dilution andmixing mode and a cleaning high speed spinning mode, but it is aseparate removable piece from the system in a preferred embodiment. Asshown in the FIG., the spindle 622 and nested dilution well 625 arecentered in the chamber 611 relative to imaginary longitudinal axis l.Preferably, the dilution well 625 is a non-wettable material, such aspolypropylene, to facilitate water removal from the well 625. In analternate arrangement, the dilution well 625 can be formed integrallywith the spindle 622.

The dilution well 625, as illustrated as a tube insert in the FIG. 6,includes an elongate tapered, hollow cylindrical section 625' having anopening 631 at its upper end 632 and terminating in a closed lower end633. The tapering or draft angle of the inner surface 625" of thedilution well tube 625 preferably is about 2° such that the tube's innerwalls 625" slope slightly outward away from axis l. The taperfacilitates creep of the waste fluids out of the bottom of the tube 625up to the opening 631 during a high speed cleaning mode. A distal tip634 axially extends from the lower tube end 633 and the tip 634conformably fits within the gripping recess 624 formed in spindle 622which effectively forms a grip by the spindle 622 on the dilution well625. The upper end 632 of the dilution well 625 also has an integralflange 637 which extends radially outward in all directions and itserves as a splash guard that covers and helps protect spindle 622 andmotor 628/drive 629 system from fluid contact during the execution ofthe cleaning mode of the dilution system 610, described in more detailelsewhere herein. The dilution well 625 also includes a plurality offins or baffles 635 integrally attached to the inner walls 625" of thedilution well 625 which project inward and effectively act as agitatorsduring fluid mixing and dilution. For example, about 3-5 equidistantlyspaced fins 635 can be used. The sample and diluent can be filled in thedilution well 625 to a depth that exceeds the height of the fins 635. Adilution well tube 625 having these features can be formed of plasticmaterial by use of conventional plastic molding techniques.

The spindle drive system preferably is capable of adjustment betweenintermittent and continuous operation modes; the intermittent mode beinguseful during mixing of the contents in the dilution well. Byintermittently energizing the motor 628 in pulses, the fluid contents ofthe tube are vigorously inter-mixed as encouraged by the fins or bafflesprovided on the inner sidewalls of the dilution well. On the other hand,the continuous high speed spinning mode is used to clean out theremaining excess fluid contents from the tube after the mixed sample hasbeen withdrawn and transferred to an assay tube for beginning the actualsample analysis. During high speed rotation, left-over fluids in thetube creep up the interior walls of the tube until they reach the mouthof the tube at which point the waste fluids are flung out of the tubeand against the inside walls of the dilution well waste chamber. Theexpelled fluids drain by gravity into the lower basin of the wastechamber and out of a drainage port into waste. Further tube cleaning canbe accomplished by the repetitive additions of wash water to the tubeduring, or followed by, spinning out the wash fluids.

An adjustable spin motor 628 preferably is used that is capable ofprecision control as to its motor speed and/or capability for relativelybrief and instantaneous energization periods. For instance, to effectmixing and dilution of a sample and specimen in the nested dilutionwell, the motor preferably is "pulsed" to achieve rapid mixing, i.e.,the motor is energized for about 100 milliseconds to put the spindle(and dilution well) in rotation, and then de-energized for about 400milliseconds such that the spindle de-accelerates and stops rapidly dueto friction, and then repeating the energization/de-energization cycleat least several times. The dilution well contents are generally pulsedin this manner about 6-8 times; although 3-4 pulses typically has beenfound adequate for homogenous mixing to be achieved. This schemeeffectively causes alternating acceleration/de-acceleration of thedilution well 625 in rotation at low average rpm's such that the fluidcontents are well agitated yet without causing the fluids to creep upthe inner walls 625" of the dilution well 625 and be prematurely flungout and spilled from the dilution well 625. The pulsed (stop-and-go)tube rotations together with the agitator-like action of the sample tubefins or baffles 635 effectively mixes the sample and diluent held in thedilution well 625 into a homogenous mixture.

A sample pipette, which interacts with but does not form part of thedilution well system per se, can then be used to extract dilute samplefrom the dilution well 625 and transfer a fraction of the diluted sampleto a reaction tube (not shown) for assay. Once the dilute sample isextracted, the dilution well tube 625 is driven in continuous rotationat high speed to cause any residual waste fluids to creep up the innerwalls 625" of the dilution well 625 to opening 631 where the fluids areflung out of the tube 625 as indicated by the arrows, which contents arecaptured within the dilution well waste chamber 611 and drained out ofdrainage port 636 at the base 621 of waste chamber 611. Wash water canbe pipetted into the dilution well 625 through aperture 631 and spunout, once or several times in succession, to further clean the dilutionwell before introduction, dilution, and mixing of the next sampletherein. For most high speed spin removal operations, the tube spin ratewill generally range from about 3,000 to about 10,000 rpm. The expelledsample, diluent or other waste fluids drain by gravity into the lowerreaches of the chamber 611 and are withdrawn for disposal via drainageport 631.

The sample dilution system of this invention is used as a subsystem ofthe immunoanalyzer used to perform immunoanalysis on a sample ofinterest in which the sample can be diluted with diluent or water andmixed into a homogenous solution in the dilution well system of thisinvention, and then withdrawing a fraction of the mixed sample viapipette and depositing same in a reaction tube (already containing thecoated bead) in which a liquid reagent is also added. The mixture ofreagent and diluted sample can then be processed according toconventional techniques such as by incubating and agitating the mixture,washing the bead, and then having a substrate (e.g., chemiluminescent)added and incubated for quantitation of analyte (e.g., by reaction tubelight output measurement).

When the inventive dilution well system is used in an immunoanalyzerinstrument, it is possible to provide user defined dilution factors forthe sample prior to analysis and to allow adjustment of the amount ofsample dilution in response to prior results where samples give resultsexceeding the valid measurement limits.

Another aspect of the inventive instrument is a unique bead dispenserdevice utilized to directly dispense a biomaterial coated bead into areaction tube with the biomaterial coated bead preserved in ahermetically-sealed environment up until it is actually dispensed into areaction tube.

Referring to the drawings, and more particularly to FIG. 7A, there isshown a bead dispenser device 700 of the invention useful for supplying,one at a time, beads for heterogenous immunoassay. The dispenser has atrack 703, formed as a coiled-ramp-like structure, capable of storingand feeding a plurality of substantially spherical beads (not shown) byeffect of gravity to a lower track end 710.

The track 703 serves as a bead support surface and has lateral outerside edges 715 which face sidewall 712 of the chamber 715 in closerproximity than the bead diameter, such as seen in the fragmentary viewof FIG. 7A, such that the inner surface of chamber sidewall 712 delimitslateral movement of a bead on the smooth supporting or lower surface 716of the track 703. The bead support surface 716 extends continuouslybetween an upper track end 709 and the lower track end 710. The track703 includes a plurality of turns between the upper track end 709 andthe lower track end 710. The provision of turns serves to effectivelylengthen the distance between the upper track end 709 and the lowertrack end 710, so that more beads effectively can be stored and suppliedalong the track 703. The turns must have enough height clearanceprovided between successive turns to avoid frictional contact with thetop of the beads. Also, the track 703 must have enough grade orinclination (angle a in FIG. 7C) provided relative to the horizontaldirection (y-direction) to allow the force of gravity to act on thebeads to overcome any frictional forces to cause the descent of thecolumn of beads down the track 703 to the lower track end 710.

In a preferred embodiment, the track 703 traces an oval-shaped, spiralpath extending from the upper track end 709 to the lower track end 710winding around a common longitudinal axis (Z-axis in FIG. 7C). Thespiral path of the track can also trace a helical path, although an ovalshape is preferred as it maximizes track space on an arcuate segment.The spiral path preferably has a constant periodicity between the uppertrack end 709 and the lower track end 710, although this is notessential, as it is only necessary to ensure adequate height clearanceis provided for the beads between successive turns of the spiral path.The track 703 is inclined at an angle a preferably between about 2° toabout 6°, and more preferably about 4°, relative to the horizontaldirection (y-axis). The selection angle α is a tradeoff betweenproviding enough clearance for the beads between successive turns of thetrack 710 and ensuring a steep enough grade for rollability of the beadsdown the track 710. In one embodiment, seen in FIG. 7F and 7A, theuppermost rung of the track 703 has an integral cover 713 having anopening 709' and a backstop 709" to permit top loading of beads. Theoval-shape of the track can have about a 15° convergence angle γ (FIG.7F) towards its smaller radius end. A central opening "c" is left insidethe track 703 for attaching the spring finger and for any desiredstorage of dessicant. The track 703 preferably is formed of moldedplastic to provide the structural features disclosed herein in anintegral structure.

Returning more specifically to FIG. 7A, an enclosure or chamber 701hermetically seals and houses the track 703 and comprises a side wall712 enclosing outer lateral surfaces 715 of the track 703, a cover 713,such as a rigid thermoplastic lid member that is ultrasonically weldedto the upper end 714 of the chamber side wall 712 after insertion of theintegral track piece 703 within the chamber 701 and loading the beads onthe track. The cover 713 hermetically seals the top end of the chamber701. Side wall 712 can be a continuous oval-shaped or cylindrical shell,such as constituted by thermoplastic material. The chamber 701 alsoincludes a base 714 including upper section 714a and a lower section714b, which together define a plunger chamber 707. The chamber 701preferably contains a dessicant material (not shown), such as locatedwithin a central open area encircled by the spiral track 703.

A first bead chamber 717 is defined by the upper section 714a of chamberbase 714 communicating with the lower track end 710 and the first beadchamber 717 being offset along the plunger chamber 707 relative to abead exit opening 708 in the lower base section 714b. The base 714 has amounting flange 725 projecting around the periphery of the bottom of thechamber 700. As best seen in FIG. 7B, opening 710', having a diameterslightly larger than the bead diameters, is provided through upper basesection 714a where opening 710' aligns with track end 710 when thespiral track 703 is inserted into chamber 701. The upraised portion offins "f" project upward from base section 714a to define first beadchamber 717 providing a short bead directing channel between the trackend 703 and the opening 710' through upper base section 714a. An opening710" is formed upper base section 714a adequate to permit insertion andmovement of spring finger 718 towards and away from opening 710'. Upperbase section 714a is upraised from medial plastic 714' joining theplunger chamber 707 to the chamber sidewall 712. Downward projectingLower base section 714b and upper base section 714 meet at medial flatplastic 714' to define the plunger chamber 707 compartment.

A plunger 702 is inserted into plunger chamber 707 and is capable ofhorizontal, reciprocal movement within the plunger chamber 707. Asbetter seen in the side fragmentary view of FIG. 7E, plunger 702 is arigid material, such as metal, wood, composite, or hard plastic, with,one end, ahead 702a and collar portion 702f capable of horizontalmovement within the larger recess 722 in chamber base 714, with movementdelimited rightward, as seen in FIG. 7A, by flange 719 in the inner wallof plunger chamber 707 of chamber base 714. On the opposite end ofplunger 702 there is a distal neck 702e sized to enter flange 723 ofbase section 714 and to slidably conform to the smaller recess 721defined in chamber base section 714. The distal neck 702e adjoinsshoulder portion 702h via collar portion 702g. The collar portions 702fand 702g have O-rings 705, 706, respectively, fitted thereon. Collarportion 702f, as with medial section 702c, is rectangular in crosssection. Therefore, for the embodiment illustrated, the O-ring 705fitted on collar 702f assumes a substantially rectangular profile whenmounted. The O-ring 706 is circular in profile when mounted on collar702g.

In the medial section 702c of the plunger, a recess 702d is provided toengage a fingered (free) terminal end 718 of a spring 719, described ingreater detail elsewhere herein. The medial section 702c of plunger 702also has throughhole 702b that is sized large enough to permitunrestricted movement of a single bead 720 (shown in phantom lines inFIG. 7A) to enter, temporarily reside within, and egress the throughhole702b. As can be understood from an objective of the invention ofproviding biomaterial coated beads to reaction tubes, it is importantthat the throughhole 702b have size adequate to accommodate a singlebead, but no more, so that each reaction tube receives one and only onebead when ejected from the dispenser device.

The plunger 702 is depicted in its at rest mode, i.e., non-actuatedmode, in FIG. 7A, whereby bead exit opening 708 is closed or blocked bya solid portion of the plunger 702. That is, the plunger 702 has athrough-hole 702b defining a second bead chamber 702b. This throughhole702b is normally aligned with the first bead chamber 717 at the lowertrack end 710 and with a plunger portion 702a concurrently blocking theexit opening 708 via a biasing means.

The biasing means is depicted as a spring 719, such as a moldedpolypropylene plastic blade-like member, terminating at its lower end ina spring finger 718 that imposes a horizontal bias force on the plunger702 (rightward in the perspective of FIG. 7A). FIG. 7A shows the sideprofile of the blade-like spring 719. The spring 719 has a medialportion "m" extending substantially perpendicularly through an openingin the enclosed central portion of the spiraled track 703 relative tothe longitudinal axis of the plunger 702 from an upper end 704 attachedphysically to the track 703, down to the free end 718. The spring finger718 normally biases the plunger 702 in the position seen in FIG. 7A withhorizontal force acting upon the plunger in the direction rightwardtoward section 702e. The spring means 719 preferably is a discreteplastic elongated piece, such as made of molded polypropylene, which isrigid yet which will tend to flex or spring back to it original positionif deflected at its unfixed end. As seen in FIG. 7F, the upper end 704of spring 719 is mechanically snapped into flanges 704' formed on theinner periphery of central opening "c" inside track 703 in order tomechanically attach the top end 704 of spring 719 to the track 703. Thespring 719 is effectively activated during the assembly of the track 703and spring 719 with the integral chamber 701 and base 714 (housing theplunger 702) in the following manner. During assembly, the plunger 702is inserted plunger chamber 717. The spring 719 is mechanically snappedinto place at its upper end 704 to the track 703. Then, the track 703and spring 719 are inserted within plunger chamber 707 until the fingerlatch 718 slides into the notch 702d in the plunger 702 and exerts arightward pushing force on the plunger 702 (in the perspective of FIG.7A) until the plunger shoulder 702h abuts flange 723 of plunger chamber707 via intervening O-ring 706. As shown in FIG. 7A and 7D, the notch702d has beveling at it upper right end to facilitate entry of fingerlatch 718 into notch 702d.

In the use of the dispenser device of the invention, exit opening 708 ofthe dispenser device is positioned directly over a mouth of a reactiontube, then an external force (not shown) is applied to the outer end ofsection 702e of plunger 702 that is sufficient in magnitude to overcomethe internal opposing biasing force of spring 704, so as to displace theplunger 702 leftward (in the view of FIG. 7A) a distance sufficient toalign bead chamber 702b of the plunger with exit opening 708, at whichpoint the bead contained and waiting in bead chamber 702b drops by theforce of gravity out of the bead chamber, through exit opening 708, andinto a reaction tube (or to intermediary means such as tubing used totransport the bead to a reaction tube).

After the bead drops from the plunger 702, the external force iswithdrawn and the internal bias forces imposed by spring end 718 actingon abutting portion 702h of plunger 702 causes the plunger 702 toretract to its original position shown in FIG. 7A. Then, as thethroughhole 702b re-aligns with the bead chamber 717 at the lower trackend 710, the next bead that had been waiting in bead chamber 717 willdrop by the force of gravity and by virtue of the weight of the columnof beads there behind, into the now vacant throughhole 702b of plunger702. As the successive bead drops into throughhole 702b, another beadsuccessively moves down to bead chamber 717 at the track end 710 to takeits predecessor's place, and so on, for each ejected bead, until thesupply of beads is exhausted, the remaining beads deemed expired, or soforth.

To ensure that the chamber 701 is hermetically sealed, O-rings 705 and706 each are insert molded onto the collar portions 702f and 702g,respectively, of plunger 702 which sealingly engage flanges 724 and 723,respectively, of the plunger chamber 707 of the base section 714. Theflange 723 of plunger chamber 707 is inclined at an acute angle ofapproximately 60° from vertical. By contrast, flange 724 of plungerchamber 707 is inclined at a relatively sharper acute angle ofapproximately 30° from vertical. As a consequence, overtravel of theplunger 702 is permitted in that a "soft stop" is created at O-ring 706on the more gentle slope presented by the surface flange 723. Again, thereturn of plunger 702 after completing a dispensing of a bead is broughtabout by the bias action of spring 719. In any event, the O-ring 706contacts flange 723 before O-ring 705 contacts flange 723 by properdimensioning of the components involved such that O-ring 706 can besqueezed during return of the plunger 702 after dispensing of a bead andremoval of actuation force on plunger face 702k. This permits a variabledegree of compression of O-ring 706 against the surface of flange 723until O-ring 705 on the opposite end of the plunger 702 makes a "hardstop" with the steep surface of flange 724. This arrangement of flanges723 and 724 with O-rings 706 and 705, respectively, prevents slidingfriction from occurring between the plunger chamber 707 and the plunger702.

To impose the normal bias on plunger 702 via spring 719, when plunger702 is in the closed position depicted in FIG. 7A, the spring 719 isinclined leftward (in perspective of FIG. 7A) at an angle ofapproximately 3.5° from vertical. This angle is created during assemblyof chamber 700 where spring 719 is mechanically attached to the track703 at its upper end 704 while lower finger 718 is pushed downward suchthat it slips down inclined wall 702j of plunger notch 702h andultimately into abutment with the right vertical wall 702i definingplunger notch 702d.

To dispense a bead, a horizontal force is exerted leftward on the rightexposed face 702k of plunger distal neck 702e in opposition to andadequate to overcome the opposing normal bias force created in theinclined spring 719. As a result, the plunger 702 horizontally moves(leftward in the perspective of FIG. 7A) to ultimately align the secondbead chamber 702b with the exit opening 708 at which point the bead heldin plunger receptacle 702b drops out of the plunger 702 and exits thechamber 700 via exit opening 708.

To show the range of movement of the spring 719 during such a dispensingoperation, in FIG. 7G, spring 719 has an initial angle β₁ ofapproximately 3.5° to the vertical in its at rest position 719a and asattached at its upper end 704 to track 703 before dispensing of a beadis initiated. When the plunger 702 is actuated to dispense a bead, theplunger 702 is deflected leftward (in the perspective of FIG. 7G) adistance such that spring 719 becomes inclined at position 719b at anangle β₂ of approximately 9° to vertical at which point receptacle 702bis aligned with exit opening 708 and the bead can drop. Once theactuation force is relieved from right end face 702k of plunger 702, theflexure intrinsic to the plastic spring 719 will cause it toautomatically return back to its initial angle β₁ of approximately 3.5°to the vertical as its at rest position 719a.

The bead dispenser of this invention thus can serve the followingfunctions:

a) to protect the beads contained therein from environmentally induceddamage;

b) to package the beads in a fashion convenient for operator access andhandling;

c) to facilitate the dispensing of a single bead into each reaction tubeas needed;

d) to provide the necessary space for identification and productlabeling; and

e) to enable visual estimation of bead inventory by the operator.

To provide the ability to perform a wide variety of different types ofimmunoassays on board a common immunoassay analyzer, the bead dispenserof this invention is effectively used in combination with a plurality oflike bead dispenser devices useful for supplying beads, one at a time,for heterogenous immunoassay to a common location for addition toreaction tubes. Each such dispenser device comprising the structuredescribed herein and any given dispenser device being loaded with beadsall having the same biomaterial coated thereupon, with the proviso thatat least one or more of the bead dispensers stores a different type ofbiomaterial as coated on its beads as compared to its cohort dispenserdevices.

The rotatable bead carousel 203, such as a rotatable platform, is usedto accommodate a large number of bead dispensers of the invention, e.g.,up to about 24 or even more, each dispenser being capable of holdinglarge numbers of beads. For instance, the bead dispensers of the presentinvention typically are loaded with about 200 beads. The entire carouselpreferably is housed within a dehumidified chamber maintained at about10% relative humidity.

The bead carousel platform holding the bead dispensing devices can berotated 360° to allow any given dispenser device to be moved by anidentifying and selecting means to a bead loading station where thecarousel passes over and intersects (in a top view) the track of areaction tube loading chain.

As explained above, it is useful and practical to provide means foridentifying each of the plurality of dispenser devices, such as by areadable bar code associated with each dispenser device, and the systemfurther comprising a selecting means, such as including a bar codereader, for identifying and selecting from among the plurality ofdispenser devices. For example, vertically oriented bar codes can beapplied to each bead dispenser making it accessible to reading by adedicated CCD bar code reader. The system also includes meanselectromechanically activatable for displacing a plunger of a selecteddispenser device as positioned at the bead loading station over areaction tube to cause one bead to drop from said exit opening into themouth of the reaction tube.

In conjunction therewith, there will also be means provided foridentifying a reaction tube and its intended analyte contents andrelating the reaction tube back to the related dispenser device having agiven biomaterial bound to a surface of the beads. Such system caninclude a tube transport means capable of moving the identifiablereaction tube to a bead loading station, relating the identifiedreaction tube to a related dispenser device having a given biomaterialbound to a surface of the beads as needed to conduct the assay desiredfor the sample of interest subsequently to be added to the reactiontube. Once the related dispenser device and reaction tube are aligned atthe bead loading station, then a bead is ejected from the related beaddispenser into the reaction tube, and then the reaction tube is conveyedwith the bead out of the bead loading station to additional stations toconduct the immunoassay itself (e.g., sample and reagent addition,incubation, washing, quantitation, and so forth), and the next reactiontube is brought to the bead loading station, and the operation repeatedfor all reaction tubes to be analyzed.

In a preferred mode of using the bead dispensing system of thisinvention, when the analyzer 10 first encounters a bead dispenser of aparticular test type and serial number, the computer 12 will initializean internal database to reflect the initial number of beads in thatparticular bead dispenser. Then each time a bead is dispensed from thebead dispenser, this internal counter will be decremented. Whenever anew run is initiated, the computer 12 will verify that sufficient fresh(unexpired) beads for each test ordered are available on-board. If not,operators will be advised via VDT display or audible warning, and soforth, to add another suitable bead dispenser before leaving theinstrument 10 unattended.

Further, when the bead carousel 203 is accessed, the analyzer preferablyshould have support software to verify the availability of all requiredinformation. If any is lacking, e.g., the bar code is unreadable orthere is an absence of information about which tests to run or how torun them, the operator will be alerted immediately. As such, theanalyzer can be programmed to proceed to process all on-board specimensbefore requiring further attention. Regarding possible test specificproblems, if no beads were dispensed, an additional attempt will be madeto do so. If two beads were dispensed, the bead dispenser's bead countwill be decremented by two, a new reaction tube drawn and an additionalattempt made to dispense a bead. If the second attempt fails, operatorsare alerted immediately of the problem via both on-screen and audiblealarms. Meanwhile, the analyzer can be programmed to continue to processother test types while waiting operator intervention. As to possiblehardware problems, such as bead carousel component failures, jams,excessive humidity in the chamber, and so forth, operators are alertedimmediately of such problems via both on-screen and audible alarms.Until the operator intervenes, sampling operations will be suspended,but the tube processor operations can programmed to continue.

According to another aspect of the invention, there is an improved tubewashing system 214 (FIG. 2) provided with a high speed spinning stationhaving an chuck housed within and surrounded by a waste chamber, wherethe waste chamber serves as a receptacle for collecting and drainingwash water fluid spun out of a tube.

Referring again to the drawings, and more particularly to FIG. 8A, theregenerally is shown a tube washing system 810 provided with a high speedspinning station 820 having an angled, grooved chuck 822 housed withinand surrounded by a waste chamber 823. Further details on theconfiguration of chuck 822 will be developed hereinafter where suitable.In FIG. 8A, the high speed spinning station 820 is shown in itsnonengaged position relative to tube 840. When engaged, such as shown inFIG. 8E, the waste chamber 823 serves as a receptacle for collecting anddraining wash water fluid spun out of a tube 840. The waste chamber 823is an enclosure defined by an upper surface 824, side wall 825, and abottom surface 826 having an arcuate shape curving inward and upwardnear its center to define an aperture 828 bounded by upward projection821. The aperture 828 has a size selected permit entry of tube 840. Theport 827 communicates with a lower end of the chamber 823 to provide ameans of drainage of wash water and other fluids expelled from the tube840 during centrifugation and captured in waste chamber 823. As bottomsurface 826 has upward curving projections 821, wash fluid that isexpelled from a tube during spinning will strike chamber walls 824 and825 and then drain by gravity out of port 827 without being able toclimb up and over projections 821 at the bottom surface of the chamber823. Therefore, wash fluid will not seep out of a small gap providedbetween tube 840 and the closely confronting, but noncontacting, inwardsurfaces 821a of projections 821. The opening 828 defined by chamberprojections 821 is sized to provide a small circumferential gap "G",e.g., about 12/1000 inch clearance, between the inner surfaces ofprojections 821 and the continuous tube flange 846.

As more easily seen in FIG. 8G, the chuck 822 preferably is a bevel gearhas a body portion defined by an upper surface 822b of generallyhemispherical-shape merging into upright stem 822d, and a grooved bottomsurface 822c. As best seen in FIG. 8F, the bevel gear 822 hasalternating grooves or slots 822a and teeth 822e disposed around theentire circumference of bottom surface 822c. As seen in FIG. 8G, theseries of spaced apart teeth 822e and intervening grooves 822a angle upto hemispherical portion 822b at an angle, preferably an angle of about45°. Chuck 822 also has a central throughhole "c" capable of receivingand allowing a pipette to be passed through the chuck. The chuck 822also is formed of a rigid material, such as metal. The chuck 822 ismounted in shaft 829 for rotation and the chuck 822 distends through thetop surface 824 to reside inside the waste chamber 823. The drive shaft829 is sealed with an O-ring 830, and bearings 832 are provided betweendrive shaft 829 and support frame 831. The drive shaft 829 is driven torotate about axis z--z by a spin motor (not shown).

A pipette 833 extends through drive shaft 829 and the center of chuck822 and its dispensing tip 834 emerges from the bottom of chuck 822 adistance sufficient to permit the tip 834 to enter a tube 840 (oncelifted into chamber 823 as seen in FIG. 8E) without closely approachingor contacting the bead support 841. A solenoid wash pump (not shown)controllably delivers wash water volumes to pipette 833. The pipette 833does not spin with chuck 822 due to the provision of bushing 857 aroundpipette 833. The bushing 857 can spin while maintaining pipette 833 in acentered non-spinning position.

The tube 840 to be washed has at least one projection or ridge 843 (bestseen in FIG. 8B and FIG. 8C) upstanding from the inner surface 844 ofthe tube. Preferably, the ridge 843 gradually tapers in height and widthdownward from the upper rim 858 of the mouth 845 of tube 840 anddisappears on the inner surface 844 as it approaches the inner bottom ofthe tube 840. The ridge(s) 843, at the rim area 858, is sized in inwardprojection and width dimensions sufficient to permit sliding of theridge(s) 843 into a groove(s) 822a of chuck 822 and its nesting betweentwo adjoining chuck teeth 822e. The inter-fit of the ridge 843 and chuckgroove 822a preferably should be provided with close clearances as loosefits may cause wear on the ridges 843 or chuck teeth 822e.

For example, in the illustrations of FIGS. 8B and 8C, three ridges 843have been provided on the inner surface 844 of test tube 840, whichridges can be nested between three pairs of teeth in chuck 822 toprovide means of temporarily physically and mechanically interlockingthe tube 840 and chuck 822 when the tube 840 is engaged (lifted into)chamber 823 such as shown in FIG. 8E. Preferably a plurality of ridges843, e.g. three or more, will be formed on the inner side 844 of thetube 840 as equidistantly spaced around the inner circumference of thetube 840. The ridges 843 preferably will have a draft angle of about0.5°, while the tube surface 844 has a draft angle of about 2° toprevent nesting of the tube in a bulk hopper.

The number of ridges 843 will be less than the total number of grooves822a provided in chuck 822. Therefore, at least one, and preferably aplurality, of grooves 822a will remain unobstructed by any ridge 843 oftube 840 during tube spinning, and thus remain available as escape pathsfor wash fluids being expelled from the tube 840 during spinning withinthe waste chamber 823.

The tube 840, at its bottom end, preferably is provided with acontinuous circular sleeve 847 extending downward and defining a recess849 in its bottom surface to permit handling by a lifting means holder,described in greater detail hereinafter. The tube 840, at its top end,preferably has a continuous flange means 846 provided on its outer sidewall. The tube 840 is supported and oriented for alignment of tuberidges 843 with chuck grooves 822a by tube conveyor chain link 848 whenthe tube 840 is nonengaged (nonlifted) relative to the high speedspinning station 820, such as shown in FIG. 8A.

To form the ridges 843 and continuous flange 846 integral with reactiontube 840, reaction tube 840 can be injection molded withstyrene-butadiene copolymer, such as "KRO3", commercially available fromPhillips 66 Co, Bartlesville, Okla. 74004.

The reaction tube 840 is lifted (and retracted) vertically along thez--z axis direction via tube elevating means 850, such as shown in FIG.8A. Tube elevating means 850 includes a tube holder 851 which holds andretains tube 840 during lift of tube 840 into waste chamber 823. Asshown in FIG. 8H, the tube holder 851 is a hollow metal tube 852 dividedat its upper half by four slots "s" extending from the top end "t" toabout halfway down the length of tube 852. This defines four 90°quadrants at the top end "t" of tube 852 and the tube is flanged orhooked by bending outward at top end "t". The tube 852 preferably isberyllium-copper alloy, which provides good spring-like flexureproperties. As seen in FIG. 8E, the flanged top "t" of tube 852interfits recess 849 of the bottom of the tube 840, such that posts 847of tube 840 can slide over the outer flanged periphery at the top "t"the tube 852 with continuous circular tube holder sleeve 853 sliding inopposition over the outer sides of the tube posts 847. The flangedportion "t" of tube 852 is slightly oversized relative to recess 849 intube 840 for positive retraction. The tube elevating means 850 includesbearings 854 permitting free rotation of the tube holder 851 relative totransfer block 856. The tube elevating means 850 further includes areciprocal shaft 855, which is vertically moveable in the z--z axisdirection, where the shaft 855 is connected to a lift motor (not shown).The lift motor, when actuated, will drive the shaft 855 verticallyupward to interfit tube holder 851 with the bottom of tube 840, assupported and oriented by a chain link of a tube conveyor 848, andcontinue to lift the tube 840 to a height until it enters waste chamber823 and tube ridge(s) 843 slides into and mate with chuck groove(s)822a. At this point, as shown in FIG. 8E, the tube 840 is engaged withhigh speed spinning station for washing and spinning. The flanges 846 ofthe tube 840 present an outer profile diameter that is less than thediameter of aperture 828 defined by bottom surface 826 of the wastechamber 823.

Once the tube 840 is so elevated into the chamber 823 effective tomechanically interlock with the chuck 822 via mating of tube ridge(s)843 and chuck groove(s) 822a, the tube 840 is rotated on its verticalaxes z--z by driving the chuck 822 in rotation while the tube issupported at the bottom of the tube (847, 849) via freely rotatableholder 851 which rotates as dictated by the movement of the chuck.During rotation, fluids are expelled from the tube 840 into the wastechamber 823 through the grooves 822a in the chuck 822, while allowingthe retention of any immunoreceptive bead 841 held within the tube 840.For most wash applications, the tube spin rate will generally range fromabout 3,000 to about 10,000 rpm.

When rotation ceases, the expelled waste fluids drain by gravity intothe lower basin 826a of the waste chamber 823 and are withdrawn fordisposal via drainage port 827. Washing can be accomplished by theaddition of water to the tube 840 during, or followed by,centrifugation. Wash water is added to the assay tube 840 via a solenoidwash pump (not shown) delivering volumes of wash water to pipette 833which pipettes the volumes of water straight down into assay tube 840.Although not particularly limited to such, in a preferred operation,multiple 400 μL volumes of water (e.g. four) are pipetted into the assaytube 840. After each addition, the wash water is almost instantaneouslyremoved after washing the inert support 841 with the bound biomaterialby high speed rotation of the tube 840.

Once the washing and centrifugation are completed for a given tube 840,the tube can be lowered via the tube elevating means 850 by retractingits shaft 855 with the tube ridge(s) 843 sliding back out of the chuckgroove(s) 822a and the tube 840 eventually clearing the waste chamber823.

After washing, the reaction (or assay) tube 840 and inert support 841will be free of unbound labeled reagent so that only bound labeledreagent will be detected.

After completion of the washing operation, the washed tubes aretransferred to a detection station for quantification of the analyte ofinterest, such as by chemiluminescent techniques described in U.S. Pat.No. 5,316,726, which is incorporated herein by reference.

The use of the tube washing system 810, such as shown in FIG. 8E,greatly facilitates the washing operation required in performing animmunoasssay and represents a significant improvement over the use ofaspiration equipment in an automated immunoassay analyzer environment.In particular, removal of the sample and wash fluid in theabove-described manner allows the wash operation to be performed rapidlyand facilely.

While the invention has been described in terms of its preferredembodiments, those skilled in the art will recognize that the inventioncan be practiced with modification within the spirit and scope of theappended claims.

What is claimed is:
 1. An automated immunoassay analyzer, comprising; aninstrument which includes(i) means for receiving a plurality of sampletubes containing a fluid sample to be assayed, wherein said sample tubereceiving means comprises at least one sample tube rack supported on arotatable sample tube carousel; (ii) means for supplying a plurality ofreaction tubes in which an assay on said samples can be performed; (iii)inert support supply and dispensing means for receiving a plurality ofinert support dispensing packs each storing a single type ofbiomaterial-coated inert support, said biomaterial capable ofselectively binding an analyte of interest in a sample, and saiddispensing packs capable of storing and dispensing said supports,individually, into a reaction tube at a support dispensing station,whereby a plurality of different biomaterial coated supports storedon-board said analyzer can be selected from for addition to saidreaction tube for performing a particular assay in said reaction tube,and said inert support supply and dispensing means comprises a rotatableinert support pack carousel; (iv) means for receiving a plurality ofreagent storage packs capable of storing and permitting reagentwithdrawal, in a self-sealing manner, whereby a plurality of differentreagents stored on-board said analyzer can be selected from for additionto said reaction tube for performing a particular assay in said reactiontube, wherein said means for receiving a plurality of reagent storagepacks comprises a rotatable reagent pack carousel; (v) means forpipetting sample and means for pipetting reagent into a supportcontaining reaction tube at a reaction tube pipetting station; (vi) anincubating station for incubating reaction tubes received from saidreaction tube pipetting station containing sample, reagent and inertsupport; (vii) a washing station for washing bound biomaterial in saidreaction tubes after said reaction tubes have been incubated at saidincubating station; (viii) a detection station for detecting a quantityof analyte bound to said biomaterial in said reaction tubes after saidreaction tubes have been washed at said washing station, said detectionstation producing a signal proportional to the quantity of analyte foreach reaction tube; (ix) a reaction rube transport pathway connecting,in this sequence, said reaction tube supply means, said inert supportsupply and dispensing means, said reaction tube pipetting station, saidincubating station, said washing station and said detection station; (x)means for identifying said sample tubes and said reagent packs on-boardthe analyzer; (xi) means for identifying said inert support dispensingpacks said means for identifying said inert support dispensing packscoordinating with said means for identifying said simple tubes and saidreagent packs such that each sample of said plurality of samples andappropriate types of reagent and biomaterial-coated inert support forsaid each sample of said plurality of samples are provided to saidreaction tubes; (xii) control means for automatic controlling of variouscomponents of said analyzer in a coordinated manner and being capable ofexecuting assay selection orders for each sample of said plurality ofsamples by selecting and coordinating the introduction of a particulartype of reagent and particular type of biomaterial-coated inert supporteffective to perform a particular requested assay on said each sample ina reaction tube, wherein said control means further coordinates saidappropriate types of reagent and said appropriate types ofbiomaterial-coated inert support effective to perform other particularrequested assays on further samples of said plurality of samples in saidreaction tube, and whereby said sample tube carousel said reagent packcarousel and said inert support pack carousel are independentlyrotatable relative to each other; and (xiii) means for determining, anddisplaying and/or recording the concentration of the analyte in aparticular sample based on said signal produced and detected at saiddetection station.
 2. The automated immunoassay analyzer of claim 1,wherein each of said rotatable sample tube carousel, said rotatablereagent pack carousel, and said rotatable inert support pack carousel,are associated with a bar code reader, whereby said control means cancontrollably track and advance said sample tubes to said samplepipetting means, said reagent packs to said reagent pipetting means, andsaid inert support dispensing packs to said inert support dispensingstation.
 3. The automated immunoassay analyzer of claim 1, wherein saidcontrol means includes a computer connected to said analyzer via datacommunication lines.
 4. The automated immunoassay analyzer of claim 3,wherein said computer is connected via data communication lines to (a) adisplay means which visually displays operator commands and datacollected from the instrument, and (b) a keyboard allowing input ofpatient information associated with test samples.
 5. The automatedimmunoassay analyzer of claim 3, wherein said analyzer includesmicroprocessing means on-board the analyzer directing operation of saidanalyzer.
 6. The automated immunoassay analyzer of claim 1, wherein saiddetection station includes a means for detecting light.
 7. The automatedimmunoassay analyzer of claim 6, wherein said means for detecting lightis a photomultiplier tube.
 8. The automated immunoassay analyzer ofclaim 1, wherein said sample container rack comprises:a base; a samplecontainer holder slave, including:a cylindrical-shaped shell defining asidewall structure, an upper opening, and an interior space, and saidshell being oriented vertically relative to said base and including avertically extending slot opening in said sidewall structure, and aplurality of sample container gripping means attached to said sidewallstructure each having at least one projection tab resiliently urgedinward, said projection tabs capable of gripping a sidewall of a samplecontainer inserted into said shell to maintain said sample container ina centered, upright orientation.
 9. The automated immunoassay analyzerof claim 1, wherein said inert support supply and dispensing meanscomprises:(1) a plurality of bead dispenser devices supported on acommon bead dispenser device carousel capable of rotation, wherein eachdispenser device comprises(a) a track capable of storing and feeding aplurality of substantially spherical beads by effect of gravity to alower track end, (b) an enclosure sealingly housing said track,comprising:a side wall enclosing outer lateral surfaces of said track, acover sealingly enclosing an upper track end of said track and upper endof said side wall, and a base including upper and lower sectionsdefining a plunger chamber, and a first bead chamber defined in saidupper section communicating with said lower track end and said firstbead chamber being offset along said plunger chamber relative to a beadexit opening in said lower section, (c) a plunger sealingly provided insaid plunger chamber and being capable of horizontal reciprocal movementwithin said plunger chamber, said plunger having a throughhole defininga second bead chamber normally aligned with said first bead chamber atsaid lower track end and with a plunger portion concurrently blockingsaid exit opening via a biasing means imposing a normal horizontal biasforce on said plunger, wherein when a horizontal force is exerted inopposition to and adequate to overcome said normal bias force saidplunger being capable of horizontal movement to align said second beadchamber with said exit opening, said normal horizontal biasing force ofsaid biasing means capable of horizontally moving said plunger effectiveto reblock said exit opening upon removal of said opposing force; and(2) identifying means for identifying each of said bead dispenserdevices.
 10. The automated immunoassay analyzer of claim 1, wherein saidmeans for storing reagent packs comprises:a plurality of reagentcontainers removably fitted onto a common reagent carousel, each saidreagent container comprising:a vessel having a plurality of separatecompartments defined by sidewalls and a cover as an upper surface, eachcompartment having an opening in said upper surface; a self-sealing lidattached to the exterior of a sidewall of said vessel, comprising:afirst arm confronting said upper surface of said vessel, said first armsupporting a plurality of caps interspaced by openings extending throughsaid arm, said first arm capable of reciprocal movement over said uppersurface of said vessel to permit covering and uncovering of saidcompartment openings by said caps, a second arm confronting saidexterior sidewall of said vessel, said second arm having a lower endattached to said sidewall of said vessel and an upper end connected tosaid first arm via a first hinge, guide means maintaining reciprocaldisplacement of said first arm along a single horizontal line ofmovement, and whereby said first arm of said lid is subject to a normalbias force created by said second arm whereby said plurality of capsnormally covers said compartment openings, wherein when a horizontalexternal force is exerted in opposition to and adequate to exceed saidnormal bias force said first arm being capable of horizontaldisplacement adequate to uncover said caps from said compartmentopenings, and upon removal of said horizontal external force said normalbias force acting on said first arm of said lid to re-cover saidcompartment openings with said caps.
 11. The automated immunoassayanalyzer of claim 1, wherein said washing station comprises:a tubespinning station havinga rotatable chuck, wherein said chuck comprises abody portion and a plurality of spaced apart teeth defining interveninggrooves extending through said body portion with at least one of saidgrooves permitting passage of fluid through said body portion and atleast one other of said grooves providing means to receive andmechanically connect a projection on an open end of a tube, a fluidwaste chamber housing said chuck, and said waste chamber comprises meansto collect and drain fluid, and an aperture defined in a lower side ofsaid chamber having a size effective to permit entry of a tube into saidchamber, a pipette for dispensing wash water into a tube, said pipettelocated centrally within said chuck, and drive means to rotate saidchuck.
 12. The automated immunoassay analyzer of claim 1, wherein saidmeans for receiving a plurality of sample tubes containing a fluidsample to be assayed further receives tubes containing diluent material,and said analyzer further comprising a sample dilution station,comprising: (a) a dilution tube well capable of receiving sample anddiluent via said sample pipetting means, and (b) means on-board theanalyzer to rotate said dilution tube well sufficient to form ahomogenous mixture, wherein said sample pipetting means being capable oftransferring portions of said mixture to reaction pipetting station, andsaid dilution well rotation means capable of high speed rotation of saiddilution tube well to eliminate excess mixture fluid, and (c) meanson-board the analyzer for catching said mixture fluid expelled duringsaid high speed rotation.
 13. The automated immunoassay analyzer ofclaim 12, wherein said sample dilution system further comprises, incombination:a dilution well waste chamber defined by (a) a chamber bodyhaving inner sidewalls and a bottom defining a space, wherein saidbottom includes a drainage port and a centrally located opening, and (b)a dilution well-cover having a central hole, said dilution well coverbeing removably fitted upon said dilution well body to cover said space;a dilution well, including:an elongated hollow cylinder having insidewalls, an upper end and an lower end, said upper end having an openingand said lower end having a plurality of inward projecting fins integralwith said inside tube walls; a dilution well spinning means, including:aholding means for conformably receiving and supporting said dilutionwell, a drive means capable of effecting rotation of said holder andsaid dilution well.
 14. An automated immunoassay analyzer,comprising:sample tube receiving member which receives a plurality ofsample tubes filled with fluid samples to be analyzed; reaction tubereceiving member which includes a plurality of reaction tubes in whichimmunoassay assay reactions are conducted; sample transfer station fortransferring at least a portion of said fluid sample from one of saidsample tubes into one of said reaction tubes; a plurality of inertsupports, each having associated therewith one of a plurality ofdifferent biomaterial specific for binding one of a plurality ofdifferent analytes; a first scanner identifying said plurality ofdifferent biomaterial; dispenser for dispensing a selected on of saidplurality of inert supports into said one of said reaction tubes; aplurality of reagents used in a plurality of different immunoassays; asecond scanner for identifying each fluid sample of said plurality offluid samples and said plurality of reagents said second scannercoordinating with said first scanner such that each fluid sample of saidplurality of fluid samples and appropriate types of reagent andbiomaterial for said each sample of said plurality of samples areprovided to said reaction tubes; reagent transfer station fortransferring at least one of said reagents into said one of saidreaction tubes based on a selected one of said plurality of inertsupports dispensed into said reaction tube by said dispenser; incubationstation for incubating a sample, an inert support and a reagent in saidone of said reaction tubes; washing station for washing said inertsupport; detection station for detecting analyte bound to said inertsupport; indicator for indicating a concentration of analyte detected atsaid detection station; sample tube identifier for identifying each of aplurality of sample tubes; inert support identifier for identifying eachof a plurality of inert supports; reagent identifier for identifyingeach of a plurality of reagents; and computer controller whichinterfaces with said sample tube identifier, said inert supportidentifier, said reagent identifier, said dispenser, said first andsecond scanners, and said reagent transfer station, said computercontroller being programmable to permit said analyzer to perform one ora plurality of different immunoassays on each of a plurality of samplesin said plurality of sample tubes, said computer controller controllingwhich of a plurality of immunoassays are conducted on a sample of saidplurality of samples in said one of said reaction tubes by selectingsaid inert support dispensed by said dispenser and said reagenttransferred at said reagent transfer station, wherein said computercontroller further coordinates other types of reagent and other types ofbiomaterial effective to perform other particular requested assays onfurther samples of said plurality of samples in said reaction tubes. 15.The automated immunoassay analyzer of claim 1, wherein said pipettingsample means and said pipetting reagent means are located within acentral portion of said means for receiving a plurality of sample tubes,said pipetting sample means travels in an arcuate path between (i) aprobe washing station in the central portion, (ii) a sample pipettingstation on said means for receiving a plurality of sample tubes, (iii) adilution well and (iv) said pipetting station, and said pipettingreagent means travels in an arcuate path between (i) said rotatablereagent pack carousel and (ii) said pipetting station.
 16. The automatedimmunoassay analyzer of claim 1, wherein said pipetting sample means andsaid pipetting reagent means are located within a central portion ofsaid means for receiving a plurality of sample tubes, said pipettingsample means and said pipetting reagent means travel in an arcuate patheach having a radius from a single point proximate to said pipettingstation.